Nasopharynx SLR

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REPORT UPDATE:

The Associations between Food, Nutrition, and Physical Activity and the Risk of Cancer of the Nasopharynx and Underlying Mechanisms

Anthony J. Alberg Kristina Boyd

Xuguang (Grant) Tao Genevieve Matanoski

Lyssa Balick Laura Caulfield

LiWei Chen Lisa Gallichio Eliseo Guallar

James G. Herman Donna Hesson Tram Kim Lam

Stephanie Mickelson Karen Robinson

Johns Hopkins University Baltimore, Maryland, USA

Completion Date June 30, 2006

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Table of Contents 1. Introduction ................................................................................................................................................ 8 2. Changes to the agreed protocol .................................................................................................................. 8 3. Results of the search ................................................................................................................................... 9 4. Description of studies................................................................................................................................ 11

4.1 Amount of data and study types.......................................................................................................... 11 4.2 Populations studied.............................................................................................................................. 11 4.3 Exposures identified / timing of exposures within the lifespan .......................................................... 11 4.4 Outcomes identified ............................................................................................................................. 12 4.5 Length of follow-up.............................................................................................................................. 12 4.6 Site-specific issues for interpretation .................................................................................................. 12

5. Results by exposures .............................................................................................................................. 13 1 Patterns of diet ................................................................................................................................... 13

1.1 Regionally defined diets ............................................................................................................. 13 1.2 Socio-economically defined diets ............................................................................................... 13 1.3 Culturally defined diets.............................................................................................................. 13 1.4 Individual level dietary patterns................................................................................................ 13 1.5 Other dietary patterns ............................................................................................................... 13 1.6 Breast .......................................................................................................................................... 14 1.6.1 Mother ........................................................................................................................................ 14 1.6.2 Child ........................................................................................................................................... 14 1.7 Other issues ................................................................................................................................ 14

2 Foods .................................................................................................................................................. 15 2.1 Starchy foods .............................................................................................................................. 15 2.1.1 Cereals (grains) .......................................................................................................................... 15 2.1.1.1 Wholegrain cereals and cereal products ................................................................................... 15 2.1.1.2 Refined cereals and cereal products .......................................................................................... 15 2.1.2 Starchy roots, tubers and plantains........................................................................................... 16 2.1.3 Other starchy foods .................................................................................................................... 17 2.2 Fruit and (non-starchy) vegetables............................................................................................ 17 2.2.1 Non-starchy vegetables .............................................................................................................. 17 2.2.1.1 Non-starchy root vegetables and tubers .................................................................................... 20 2.2.1.2 Cruciferous vegetables ............................................................................................................... 21 2.2.1.3 Allium vegetables ....................................................................................................................... 23 2.2.1.4 Green leafy vegetables (not including cruciferous vegetables) ................................................. 23 2.2.1.5 Other non-starchy vegetables .................................................................................................... 25 2.2.1.6 Raw vegetables ........................................................................................................................... 28 2.2.2 Fruits........................................................................................................................................... 28 2.2.2.1 Citrus fruit.................................................................................................................................. 29 2.2.2.2 Other Fruits................................................................................................................................ 30 2.3 Pulses (legumes).......................................................................................................................... 31 2.4 Nuts and Seeds............................................................................................................................ 33 2.5 Meat, poultry, fish and eggs....................................................................................................... 33 2.5.1 Meat ............................................................................................................................................ 33 2.5.1.1 Fresh Meat.................................................................................................................................. 35 2.5.1.2 Processed meat ........................................................................................................................... 35 2.5.1.3 Red meat ..................................................................................................................................... 36 2.5.1.3.1 Beef.......................................................................................................................................... 36

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2.5.1.3.2 Pork......................................................................................................................................... 37 2.5.1.3.4 Organ Meats ........................................................................................................................... 37 2.5.1.4 Poultry ........................................................................................................................................ 38 2.5.2 Fish (excluding salted fish)......................................................................................................... 38 2.5.2.1 Salted Fish .................................................................................................................................. 38 2.5.2.2 Other preserved fish (excluding salted fish).............................................................................. 54 2.5.3 Shellfish and other seafood ........................................................................................................ 54 2.5.4. Eggs............................................................................................................................................. 56 2.6 Fats, oils and sugars ................................................................................................................... 57 2.6.1 Animal fats ................................................................................................................................. 57 2.6.2 Plant oils ..................................................................................................................................... 58 2.6.3 Hydrogenated fats and oils ........................................................................................................ 58 2.6.4 Sugars ......................................................................................................................................... 58 2.7 Milk and dairy products ............................................................................................................ 58 2.8 Herbs, spices, condiments .......................................................................................................... 59 2.9 Composite Foods ........................................................................................................................ 61

3 Beverages............................................................................................................................................ 62 3.1 Total fluid intake ........................................................................................................................ 62 3.2 Water .......................................................................................................................................... 63 3.3 Milk............................................................................................................................................. 63 3.5 Fruit juices.................................................................................................................................. 64 3.6 Hot drinks................................................................................................................................... 64 3.6.1 Coffee .......................................................................................................................................... 64 3.6.2 Tea .............................................................................................................................................. 64 3.6.2.1 Black tea ..................................................................................................................................... 65 3.6.2.2 Green tea .................................................................................................................................... 65 3.6.3 Maté ............................................................................................................................................ 66 3.6.4 Other hot drinks......................................................................................................................... 66 3.7 Alcoholic drinks.......................................................................................................................... 66 3.7.1 Total ............................................................................................................................................ 66 3.7.1.1 Beers ........................................................................................................................................... 71 3.7.1.2 Wines .......................................................................................................................................... 72 3.7.1.3 Spirits.......................................................................................................................................... 72 3.7.1.4 Other alcoholic drinks................................................................................................................ 72

4 Food production, preservation, processing and preparation ........................................................... 72 4.1 Production .................................................................................................................................. 72 4.1.1 Traditional methods (to include ‘organic’) ................................................................................ 72 4.1.2 Chemical contaminants.............................................................................................................. 72 4.1.2.1 Pesticides..................................................................................................................................... 73 4.1.2.2 DDT ............................................................................................................................................ 73 4.1.2.3 Herbicides................................................................................................................................... 73 4.1.2.4 Fertilisers .................................................................................................................................... 73 4.1.2.5 Veterinary drugs ........................................................................................................................ 73 4.1.2.6 Other chemicals.......................................................................................................................... 73 4.1.2.6.1 Polychlorinated dibenzofurans (PCDFs) ........................................................................... 73 4.1.2.6.2 Polychlorinated dibenzodioxins (PCDDs).......................................................................... 73 4.1.2.6.3 Polychlorinated biphenyls (PCBs) ..................................................................................... 73 4.1.2.7 Heavy metals............................................................................................................................... 73 4.1.2.7.1 Cadmium ............................................................................................................................ 74

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4.1.2.7.2 Arsenic ................................................................................................................................ 74 4.1.2.7.3 Other heavy metals............................................................................................................. 74 4.1.2.8 Waterborne residues .................................................................................................................. 75 4.1.2.8.1 Chlorinated hydrocarbons ................................................................................................. 75 4.1.2.9 Other contaminants.................................................................................................................... 75 4.2 Preservation................................................................................................................................ 76 4.2.1 Drying ......................................................................................................................................... 81 4.2.2 Storage ........................................................................................................................................ 83 4.2.2.1 Mycotoxins .......................................................................................................................... 83 4.2.2.1.1 Aflatoxins ............................................................................................................................ 84 4.2.2.1.2 Others.................................................................................................................................. 84 4.2.3 Bottling, canning, vacuum packing ........................................................................................... 84 4.2.4 Refrigeration .............................................................................................................................. 84 4.2.5 Salt, salting ................................................................................................................................. 84 4.2.5.1 Salt .............................................................................................................................................. 84 4.2.5.2 Salting ......................................................................................................................................... 84 4.2.5.3 Salted foods................................................................................................................................. 84 4.2.5.3.1 Salted animal food (excluding salted fish) ......................................................................... 84 4.2.5.3.1.1 Salted fish ........................................................................................................................ 86 4.2.5.3.2 Salted plant food ................................................................................................................102 2.2.1.1 Non-starchy root vegetables and tubers ...................................................................................102 4.2.6 Pickling ......................................................................................................................................105 4.2.7 Curing and smoking..................................................................................................................106 4.2.7.1 Cured foods ...............................................................................................................................106 4.2.7.1.1 Cured meats.......................................................................................................................107 4.2.7.1.2 Smoked foods .....................................................................................................................107 4.3 Processing ..................................................................................................................................108 4.3.1 Refining......................................................................................................................................109 4.3.2 Hydrogenation...........................................................................................................................110 4.3.3 Fermenting ................................................................................................................................110 4.3.4 Compositional manipulation.....................................................................................................112 4.3.4.1 Fortification ...............................................................................................................................112 4.3.4.2 Genetic modification .................................................................................................................112 4.3.4.3 Other methods ...........................................................................................................................112 4.3.5 Food additives............................................................................................................................112 4.3.5.1 Flavours .....................................................................................................................................112 4.3.5.2 Sweeteners (non-caloric) ...........................................................................................................113 4.3.5.3 Colours.......................................................................................................................................113 4.3.5.4 Preservatives..............................................................................................................................113 4.3.5.4.1 Nitrites and nitrates...........................................................................................................113 4.3.5.5 Solvents ......................................................................................................................................113 4.3.5.6 Fat substitutes............................................................................................................................113 4.3.5.7 Other food additives..................................................................................................................113 4.3.6 Packaging...................................................................................................................................113 4.3.6.1 Vinyl chloride ............................................................................................................................114 4.3.6.2 Phthalates ..................................................................................................................................114 4.4 Preparation................................................................................................................................114 4.4.1 Fresh food ..................................................................................................................................114 4.4.1.1 Raw ............................................................................................................................................118

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4.4.1.2 Juiced .........................................................................................................................................118 4.4.2 Cooked food...............................................................................................................................118 4.4.2.1 Steaming, boiling, poaching ......................................................................................................118 4.4.2.2 Stewing, casseroling...................................................................................................................119 4.4.2.3 Baking, roasting ........................................................................................................................119 4.4.2.4 Microwaving ..............................................................................................................................119 4.4.2.5 Frying.........................................................................................................................................119 4.4.2.6 Grilling (broiling) and barbecuing ...........................................................................................119 4.4.2.7 Heating, re-heating....................................................................................................................119

5 Dietary constituents ..........................................................................................................................119 5.1 Carbohydrate ............................................................................................................................119 5.1.1 Total carbohydrate....................................................................................................................119 5.1.2 Non-starch polysaccharides/dietary fibre.................................................................................119 5.1.2.1 Cereal fibre ................................................................................................................................120 5.1.2.2 Vegetable fibre...........................................................................................................................120 5.1.2.3 Fruit fibre ..................................................................................................................................120 5.1.3 Starch.........................................................................................................................................120 5.1.3.1 Resistant starch .........................................................................................................................120 5.1.4 Sugars ........................................................................................................................................120 5.2 Lipids .........................................................................................................................................120 5.2.1 Total fat .....................................................................................................................................120 5.2.2 Saturated fatty acids .................................................................................................................120 5.2.3 Monounsaturated fatty acids ....................................................................................................120 5.2.4 Polyunsaturated fatty acids.......................................................................................................120 5.2.4.1 n-3 fatty acids ............................................................................................................................120 5.2.4.2 n-6 fatty acids ............................................................................................................................121 5.2.4.3 Conjugated linoleic acid............................................................................................................121 5.2.5 Trans fatty acids........................................................................................................................121 5.2.6 Other dietary lipids, cholesterol, plant sterols and stanols. .....................................................121 5.3 Protein .......................................................................................................................................121 5.3.1 Total protein ..............................................................................................................................121 5.3.2 Plant protein ..............................................................................................................................121 5.3.3 Animal protein...........................................................................................................................121 5.4 Alcohol .......................................................................................................................................121 5.5 Vitamins.....................................................................................................................................121 5.5.1 Vitamin A ..................................................................................................................................122 5.5.1.1 Retinol........................................................................................................................................122 5.5.1.2 Provitamin A carotenoids .........................................................................................................122 5.5.2 Non-provitamin A carotenoids .................................................................................................122 5.5.3 Folates and associated compounds ...........................................................................................122 5.5.4 Riboflavin ..................................................................................................................................122 5.5.5 Thiamin (vitamin B1) ................................................................................................................122 5.5.6 Niacin .........................................................................................................................................122 5.5.7 Pyridoxine (vitamin B6) ............................................................................................................123 5.5.8 Cobalamin (vitamin B12) ..........................................................................................................123 5.5.9 Vitamin C ..................................................................................................................................123 5.5.10 Vitamin D (and calcium) ...........................................................................................................123 5.5.11 Vitamin E...................................................................................................................................123 5.5.12 Vitamin K ..................................................................................................................................123

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5.5.13 Other..........................................................................................................................................124 5.6 Minerals .....................................................................................................................................124 5.6.1 Sodium .......................................................................................................................................124 5.6.2 Iron ............................................................................................................................................124 5.6.3 Calcium (and Vitamin D)..........................................................................................................124 5.6.4 Selenium ....................................................................................................................................124 5.6.5 Iodine .........................................................................................................................................125 5.6.6 Other..........................................................................................................................................125 5.7 Phytochemicals ..........................................................................................................................127 5.7.1 Allium compounds.....................................................................................................................127 5.7.2 Isothiocyanates ..........................................................................................................................127 5.7.3 Glucosinolates and indoles ........................................................................................................127 5.7.4 Polyphenols................................................................................................................................127 5.7.5 Phytoestrogens eg genistein.......................................................................................................127 5.7.6 Caffeine......................................................................................................................................127 5.7.7 Other..........................................................................................................................................127 5.8 Other bioactive compounds ......................................................................................................127

6 Physical activity ................................................................................................................................128 6.1 Total physical activity (overall summary measures)................................................................128 6.1.1 Type of activity ..........................................................................................................................128 6.1.1.1 Occupational..............................................................................................................................128 6.1.1.2 Recreational...............................................................................................................................128 6.1.1.3 Household ..................................................................................................................................128 6.1.1.4 Transportation ..........................................................................................................................128 6.1.2 Frequency of physical activity ..................................................................................................128 6.1.3 Intensity of physical activity .....................................................................................................128 6.1.4 Duration of physical activity .....................................................................................................128 6.2 Physical inactivity......................................................................................................................128 6.3 Surrogate markers for physical activity e.g. occupation .........................................................128

7 Energy balance..................................................................................................................................129 7.1 Energy intake ............................................................................................................................129 7.1.1 Energy density of diet................................................................................................................129 7.2 Energy expenditure ...................................................................................................................129

8 Anthropometry .................................................................................................................................129 8.1 Markers of body composition ...................................................................................................129 8.1.1 BMI ............................................................................................................................................129 8.1.2 Other weight adjusted for height measures .............................................................................129 8.1.3 Weight........................................................................................................................................129 8.1.4 Skinfold measurements .............................................................................................................129 8.1.5 Other (e.g. DEXA, bio- impedance, etc) ...................................................................................129 8.1.6 Change in body composition .....................................................................................................129 8.2 Markers of distribution of fat ...................................................................................................129 8.2.1 Waist circumference..................................................................................................................130 8.2.2 Hips circumference ...................................................................................................................130 8.2.3 Waist to hip ratio.......................................................................................................................130 8.2.4 Skinfolds ratio ...........................................................................................................................130 8.2.5 Other e.g. CT, ultrasound .........................................................................................................130 8.3 Skeletal size................................................................................................................................130 8.3.1 Height (and proxy measures) ....................................................................................................130

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8.3.2 Other (e.g. leg length)................................................................................................................130 8.4 Growth in fetal life, infancy or childhood ................................................................................130 8.4.1 Birthweight ................................................................................................................................130 8.4.2 Weight at one year.....................................................................................................................130

F. Narrative review on mechanistic studies ................................................................................................131 6. Discussion.................................................................................................................................................134 7. References ................................................................................................................................................137Summary table......................................................................................................................................................145Results table..........................................................................................................................................................155

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1. Introduction Any evaluation of the role of diet, nutrition, and physical activity in relation to the risk of nasopharyngeal carcinoma (NPC) must account for the fact that it occurs at very high rates in a few specific regions of the world. NPC is a rare malignancy in most parts of the world, with age-adjusted incidence rates (per 100,000) of 1.7 among men and 0.6 among women, and mortality rates (per 100,000) in men and women of 1.0 and 0.4, respectively (Ferlay J., 2001). In contrast, specific high-risk areas include Hong Kong, Singapore, and southern China, especially the Cantonese living in the central region of Guangdong Province. The rates of NPC are intermediate (2 to 6 per 100,000) in other areas of Southeast Asia, such as Malaysia, Vietnam, Micronesia, and Guam. Dietary factors could contribute to the striking variation in NPC rates. A prominent hypothesis is that salted/preserved foods contribute to the burden of NPC in the high risk regions. A preponderance of the evidence concerning the potential role of diet in the etiology of NPC has focused on this hypothesis. Cantonese-style salted fish has been the primary focus, but other salted and preserved foods have also been investigated. Epstein-Barr virus (EBV) is a necessary cause of NPC. If diet does contribute to NPC risk, it is thus likely to do so by acting in concert with EBV infection. Any dietary factor that alters the risk of developing NPC, either increasing or decreasing risk, is thus likely to act by altering susceptibility to EBV-induced carcinogenesis. Driven by this focus in the evidence, this SLR emphasizes the risk associated with salted/preserved foods (e.g., Cantonese-prepared salted fish). Evaluation of the potential interrelationship of this dietary exposure with the major known cause of NPC, EBV infection, could not be assessed with epidemiologic data due to a lack of data evaluating these two exposures jointly in the same study. The mechanistic review thus forms the basis for evaluating the plausibility of the observed associations. 2. Changes to the agreed protocol Four changes were made to the approved protocol. First, the bibliographic databases searched (protocol p. 13, Table 1) were modified as follows. The Biosis database was included in the Biological Abstracts Silverplatter search. The SciSearch database was included in the ISI Web of Knowledge search. The PreCinahl database was included in the Cinahl search. As recommended by WCRF, the National Research Register (NRR) was replaced by searching metaRegister. Second, the term “head and neck” was excluded from the search strategy for outcomes (protocol p. 18) because in PubMed, including the term “head and neck”: 1) led to a 2.5-fold increase in the number of records and 2) did not add value to the search, as a check on a random sample of 200 records that included the items “head and neck” showed that none would have been judged relevant for full text retrieval. Third, ancillary searches of potential confounders or effect modifiers (protocol p. 19) were not performed. Instead, confounders and effect modifiers were incorporated into each phase of the overall search strategy as suggested by WCRF. Fourth, data extraction took place using serial rather than duplicate review for the majority of papers. Following the revised guidelines from WCRF (see: Section 3. Further instruction/clarifications to SLR centres 21/05/04), duplicate reviews were carried out the first twenty reviews and all studies with prospective dietary

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assessment, sorted out the coding differences, and then proceeded to serial extraction of the data for the remainder of the papers. Fifth, we did attempt to adhere to the revised guidelines concerning forest plots and meta-analyses. 3. Results of the search The following three steps were taken in the search strategy: 1) electronic searches of non-Chinese bibliographic databases; 2) electronic searches of the Chinese Biomedical Literature Database System (in Chinese); and 3) hand searching. These steps resulted in the identification of 5,224 potentially relevant unique (non-duplicate) articles, as summarized in Table 1. Of this total, 97.6% were identified in step #1, 0.8% in step #2, and 1.6% in step #3. The 5,098 articles identified in step #1 were ascertained via the following databases: PubMed, 57.9% (n=2,951); Embase, 6.7% (n=1,360); Pascal, 6.8% (n=349); Biological Abstracts, 3.9% (n=198); ISI, 3.4% (n=172); EbscoHost, 0.4% (n=20); NIAA, 0.3% (n=17); Cochrane, 0.2% (n=11); LILACS, 0.2% (n=10); IMSEAR, <0.1% (n=5); Agricola, <0.1% (n=3); and IMEMR, <0.1% (n=2). The 84 unique articles identified by hand searching (step #3) were found by checking references in: the data extraction articles (49%), reviews and meta-analyses ascertained via a PubMed search (45%), and the 1997 WCRF report (6%).

Table 1. Summary of the literature search

Database Date Searched Records Found Duplicates Detected Unique Records Imported

PubMed 01/24/2006 2961 10 2951 Embase 03/13/2006 3234 1874 1360 ISI Web of Science 04/11/2006 749 577 172 Biological Abstracts – Silverplatter 04/20/2006 405 207 198 Pascal – Silverplatter 04/20/2006 1417 1068 349 NIAAA Alcohol and Alcohol Problems Science Database

04/20/2006 28 11 17

Agricola 04/20/2006 22 19 3 Cochrane Library - Cochrane Collaboration (Central)

04/20/2006 13 2 11

CINAHL – EBSCOhost 04/20/2006 28 8 20 LILACS – Latin American and Caribbean Center on Health Sciences Information

04/20/2006 12 2 10

IMEMR – Index Medicus for WHO Eastern Mediterranean Region

04/20/2006 2 0 2

IMSEAR – Index Medicus for South East Asian Region

04/20/2006 6 1 5

Chinese Biomedical Literature Database System 4/04-6/04 202 160 42 Hand Searching 10/2005 84 N/A 84 Totals (as of 06/30/06) 9163 3939 5224 Upon duplicate abstract review, 624 (11.9%) of the 5,224 unique articles identified were not excluded and proceeded to full text review (Figure 1); 537 (86.1%) from step #1, 42 (6.7%) from step #2, and 45 (7.2%) from step #3. Reasons for exclusion of articles based on the abstract reviews are summarized in Table 2.

Figure 1. Flowchart for review results.

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Table 2. Reasons for exclusion of abstracts (n=4,600) from abstract reviews.

Reason for exclusion N Percent No evidence on the association between exposures and NPC. 3,192 69.4 Research at the cellular level only. 311 6.8 Research in animal models. 95 2.1 Mentions EBV, Tobacco, or other confounders only. 110 2.4 Not peer reviewed. 24 0.5 Meta analysis. 8 0.2 No original data. 156 3.4 Cancer survivors only. 199 4.3 Other 505 11.0

Upon duplicate full text review, 80 (12.8%) of the 624 unique articles not excluded from the abstract review were not excluded from the full text review; 58 (72.5%) from step #1, 17 (21.2%) from step #2, and 5 (6.3%) from step #3. There were 2 were potentially relevant articles that could not be obtained. The reasons for exclusion of full text articles for are summarized in Table 3.

Table 3. Reasons for exclusion of full text articles (n=542).

Reason for exclusion N Percent No evidence on the association between exposures and NPC. 160 29.5 Research at the cellular level only. 8 1.5 Research in animal models. 1 0.2 Mentions EBV, Tobacco, or other confounders only. 18 3.3 Meta-analysis 1 0.2 No original data. 86 15.9 Cancer survivors only. 14 2.6 Non-specific anatomy (mentions nasal, pharynx, etc. but no NPC) 213 39.3 Other 41 7.6

Of the 80 articles not excluded after full text review, a total of 74 articles met the eligibility criteria for data extraction for the SLR, 54 from step #1, 17 from step #2, and 3 from step #3. Six articles were case only studies with no genotype reported and therefore were not extracted.

5,224

Unique articles identified from

literature search

624

Articles not excluded after

duplicate abstract review

4,600

Articles excluded after


542


duplicate full text review

80



2

Articles could not be

obtained

5,224

Unique articles identified from

literature search

624



4,600



542



80



2

Articles could not be

obtained

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4. Description of studies 4.1 Amount of data and study types There were 75 studies from the 74 articles extracted; one article reported an ecological study and a cross-sectional study (Li, 1996). Of the 75 studies, the distribution of study designs was: 56 (75%) case-control, 15 (20%) ecological, 2 (3%) historical cohort, 1 (1%) prospective cohort, and 1 (1%) cross-sectional. 4.2 Populations studied The studies were concentrated in Asia (79%), particularly China (63% of studies, 57% of case-control studies). Ten studies (8 case-control and 2 ecologic) were conducted in the U.S.A.; no other non-Asian countries had more than one study. 4.3 Exposures identified / timing of exposures within the lifespan As can be seen from the summary of evidence for key exposures in Appendix 2 (Summary Tables), this systematic review identified evidence only relevant to the association between diet and nutrition and NPC. No results for physical activity, energy balance, or anthropometry were observed. The exposures identified were predominantly related to preserved foods, particularly salting. The most commonly studied exposure was salted fish. The intake of salted fish during different age windows (e.g., weaning/early childhood (0-3 years), later childhood (3 to 10 years), and adulthood has been studied; dose-response meta-analyses were performed for these exposure windows. One other key exposure in which a dose-response analysis was possible was total alcohol (1 cohort study, 18 case-control studies). Only adulthood consumption for this exposure was available for dose-response meta-analysis. Key exposures in which highest-versus-lowest category analysis was possible were non-starchy vegetables during adulthood (5 case-control studies, 2 ecological studies), carrots during childhood (6 case-control studies), tomatoes during adulthood (5 case-control studies), preserved vegetables during adulthood (5 case-control studies), citrus fruits during adulthood (5 case-control studies), processed meat during adulthood (5 case-control studies), herbal intake (6 case-control studies), and tea during adulthood (7 case-control studies). Other exposure categories with 5 or more case-control/cohort studies, but not eligible for meta-analysis include: total preserved vegetables during adulthood (7 case-control studies), non-preserved cruciferous vegetables during adulthood (5 case-control studies) and childhood (6 case-control studies), preserved cruciferous vegetables during adulthood (5 case-control studies), other preserved vegetables during adulthood (5 case-control studies), total fruits during adulthood (6 case-control studies), other non-preserved fruits during childhood (5 case-control studies), preserved plums during childhood (5 case-control studies), preserved soy/tofu during adulthood (8 case-control studies) and childhood (6 case-control studies), processed meat during adulthood (5 case-control studies), preserved fish-excluding salted fish (1 cohort, 5 case-control studies), preserved seafood during adulthood (5 case-control studies) and childhood (5 case-control studies), salted eggs during adulthood (5 case-control studies), other preserved eggs (5 case-control studies), preservation/preserved animal foods (1 cohort study, 5 case-control studies) and plant foods (12 case-control studies), drying/dried animal foods (5 case-control studies) and plant foods (5 case-control studies), salted animal food-excluding fish

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(10 case-control studies), salted plant food (9 case-control studies), pickled foods (11 case-control studies), processed foods (6 case-control studies), refined foods (6 case-control studies), fermented foods (1 cohort study, 10 case-control studies), and fresh animal foods (6 case-control studies) and plant foods (9 case-control studies). WCRF exposure categories with relatively sparse evidence included regionally and culturally defined diets, starchy foods and cereals, and micronutrients and macronutrients. 4.4 Outcomes identified This SLR focuses exclusively on nasopharyngeal carcinoma. 4.5 Length of follow-up Length of follow-up is relevant for only a few studies since the preponderance of the evidence stems from case-control (and ecologic) studies. The average length of follow-up for the 3 cohort studies was 9.2 ± 1.3 years. 4.6 Site-specific issues for interpretation When considering the possible role of diet to the etiology of nasopharyngeal carcinoma, the major methodological consideration is that NPC is a disease for which viral oncogenesis plays a central role. Specifically, Epstein-Barr virus (EBV) is considered a necessary cause of NPC. However, EBV is far from a sufficient cause, based on the following lines of evidence: 1) EBV infects the majority of the adult population not only in areas with high rates of NPC, but also in areas where NPC is uncommon (Cohen, 2000, Griffin, 2000); 2) after a primary infection with EBV, individuals remain lifelong EBV carriers, but even in regions with high NPC rates there is a small absolute risk of going on to develop NPC (Griffin, 2000). Thus, although exposure to EBV and even chronic EBV infection may be considered a necessary step in the causal pathway, these steps are far from sufficient to result in progression to clinical disease. This set of circumstances support the notion that in addition to EBV, nasopharyngeal carcinogenesis requires the presence of a “trigger” for disease progression to occur. Additional factors must modulate the risk of the development of nasopharyngeal carcinoma following EBV infection. These additional risk factors that act as “triggers” could be genetic and/or environmental exposures. Hence, if dietary factors contribute to NPC risk, they are likely to do so by acting in concert with EBV infection. Any dietary factor that alters the risk of developing NPC, either increasing or decreasing risk, is thus likely to act by altering susceptibility to EBV-induced carcinogenesis. A potentially critical element in study methodology would therefore be incorporating measures of EBV infection, such as antibody titres, into dietary studies of NPC. The literature on cervical cancer provides a useful example, as research on cervical cancer that has included measurement of infection with oncogenic strains of HPV has been important in elucidating the role of environmental factors in cervical carcinogenesis. Despite the importance of accounting for EBV infection status in studies of diet and NPC to advance our understanding of the etiology of nasopharyngeal carcinoma, very few studies have actually done so. In assessing this evidence, it is important to consider that very few studies that contributed to this systematic review accounted at all for EBV infection status. To summarize, NPC is caused by EBV, but EBV has not been accounted for in most of the evidence summarized in this report. Future research that addresses this gap would have potential to clarify the role of diet, and other environmental exposures, in relation to risk of NPC. Further refinements in approach could be envisioned, whereby timing of EBV infection in relation to exposure to dietary factors was considered, as any

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potential influence of dietary factors on EBV related carcinogenesis involving the reactivation of EBV must therefore occur temporally after primary Epstein-Barr virus infection. While epidemiologic studies with measurement of EBV infection status will be of great value, also of great importance would be studies in NPC cell lines to investigate empirical link between dietary agents and EBV reactivation, an important transforming event in NPC progression. 5. Results by exposures 1 Patterns of diet

1.1 Regionally defined diets No results found. 1.2 Socio-economically defined diets A3 Case-control studies (1) In a case-control study in Malaysia of histopathologically confirmed NPC patients ascertained from the main radiotherapy clinic in Kuala Lumpur each matched to one neighborhood control, in Chinese (OR 4.3; p-value 0.01) and Indian Malaysian (OR 9.0; p-value 0.05) cases were more likely than controls to have consumed poorer, simpler diet consisting mostly of rice with only little portions of meat, fish, vegetables, or fruit (Armstrong et al., 1983a). These data were adjusted for salted fish intake during childhood in addition to the matched factors of age, gender, residence and ethnicity. 1.3 Culturally defined diets A3 Case-control studies (1) In a preliminary report from the same case-control study of Armstrong and Armstrong in Malaysia which later formed the basis for the information reported in Section 1.2, being in a family that consumed a “multiethnic cuisine” was protective for NPC compared to being a family that adhered more strictly to the cuisine of a single ethnic group (OR = 0.2; p=<.01) (Armstrong, 1978). This association was not adjusted for any covariates. The authors interpreted this exposure to be a marker of adherence to traditional lifestyles. 1.4 Individual level dietary patterns No results found. 1.5 Other dietary patterns A3 Case-control studies (3) Three case-control studies looked at aspects of weaning and diet, including age stopped bottle-feeding, being weaned straight to an adult diet, and age at which first solid food was given. In a study of Chinese in Singapore, the risks related to age of cessation of bottle-feeding was non-significantly higher (OR 1.5; 95% CI 0.6 – 5.5) for those stopping past 24 months of age compared to those who were never bottle-fed as infants (Lee et al., 1994). Although this association was not statistically significant for the highest-versus-lowest category comparison, the authors reported that the trend was statistically significant (p=0.01). The results were adjusted for age, gender, education, and ethnicity. The maximum age of subjects in this study was 44 years.

14

The second study, conducted in Tunisia, used a food-frequency questionnaire (FFQ) to determine whether or not as children study participants were shifted to an adult diet during weaning (Jeannel et al., 1990a). The results indicated that individuals fed an adult diet at time of weaning had a statistically significant 5.1-fold (No CI, p=0.03) higher risk of NPC than those receiving a different diet, after adjusting for age, gender, residence and life style. In the third study, comprised of Chinese in China, the age of initiation of eating solid foods was investigated and the results showed that both cases and controls were fed solid foods at an average age of approximately 6 months. The results were adjusted for age, gender, and residence (Yu et al., 1989). In summary, studies of the association between weaning age in relation to risk of NPC do not lend themselves to a clear-cut conclusion. One study observed no association with age of eating solid foods (Yu et al., 1989), and the results of another suggested that later age of stopping weaning may be weakly associated with NPC risk (Lee et al., 1994). Perhaps the most intriguing findings in this regard were those of Jeannel et al (Jeannel et al., 1990a), which suggested that shifting from weaning straight to an adult diet, which may include potentially harmful constituents such as salted fish, was strongly associated with increased NPC risk. Thus, age at weaning per se may not be the key characteristic, but rather what foods are consumed around the time of weaning. 1.6 Breastfeeding No results found. 1.6.1 Mother No results found. 1.6.2 Breastfeeding--Child A3 Case-control studies (2) Two case-control studies examined the duration of being breastfed as a child. In the study in Algeria of Laouamri and colleagues, shorter durations of being breastfed as an infant were associated with NPC in the protective direction, except at the longest durations. In fact, significantly increased risk of NPC was present among those who were breast-fed for 24 months or more compared to those who were never breast-fed (OR=4.0 CI, 1.2 – 12.8) (Laouamri et al., 2001), but this result was based on an exposed group of only 12 cases and 4 controls. These data were adjusted for age, gender and residence. In a Chinese population in Singapore, duration of being breastfed was inversely associated with NPC risk. Compared to those who never breastfed, the odds ratio for NPC was 0.3 (95% CL 0.1, 0.8) among those who breastfed 1-6 months, and 0.6 (95% CL 0.2 – 1.4) among those who breast-fed for seven or more months (Lee et al., 1994). The markedly different cutpoints used to assess duration of breastfeeding in the two studies (>24 versus >7 months) makes it difficult to directly compare the results between the two studies. 1.7 Other issues A3 Case-control studies (1) One case control study examined the influence of patterns of eating meals and snacks on the risk of NPC in Chinese in Malaysia based on interview data (Armstrong, 1978). The authors noted that the unadjusted OR showed no significant association but details were not provided.

15

2 Foods 2.1 Starchy foods No results found. 2.1.1 Cereals (grains) Total Cereals: Adulthood consumption A3 Case-control studies (1) Adult consumption of corn and wheat, measured as a dichotomous “yes versus no” consumption was associated with increased risk of NPC (OR 1.53; 95% CL 1.02, 2.28) in a population-based case-control study (n=104 cases, n=104 controls) in China (Huang, 1997). This association was based on exposure three years prior to the cancer diagnosis and was adjusted for age, sex, neighborhood, and other factors. In this same study, an even stronger association was observed for the comparison of those who consumed cereals every day to those who consumed a few (OR 16; 95% CI 3.1-82.4), but this result was unadjusted. Total Cereals: Childhood consumption A3 Case-control studies (2) Two studies reported on the association between cereal consumption during childhood and NPC risk. Both of these studies were implemented in northern Africa. In Tunisia, the consumption of mhammas (cracked wheat) during childhood was associated with reduced risk of NPC (OR 0.3) for the highest-versus-lowest category comparison in a study that compared 80 NPC cases with 160 controls, but the interpretation of this association is hindered by the lack of reporting of further details (Jeannel et al., 1990a). In an Algerian study comprised of 72 cases and 72 controls, an imprecise odds ratio of 4.0 (95% CI 0.18-4.4) was observed for ever-versus-never use of cherchem during teething. Cherchem are wheat or barley pieces softened through contact with the floor and walls when stored underground (Laouamri et al., 2001). 2.1.1.1 Wholegrain cereals and cereal products A3 Case-control studies (1) A case-control study of 122 cases and 122 controls was carried out in China to investigate the association of wholegrain cereals and the risk of NPC. The results of this study were in the protective direction, with an odds ratio of 0.19 (p-value 0.02) for frequent versus infrequent consumption of wholegrain cereals after adjusting for age, sex, environmental factors and a number of dietary factors (Wang, 1993). 2.1.1.2 Refined cereals and cereal products Bread: Adulthood consumption A3 Case-control studies (3) Three case-control studies reported on the potential association between eating bread as an adult and risk of NPC. Two of these studies were carried out in China. In the first of the studies in China, Yu and colleagues observed that bread consumption during adulthood (Yu et al., 1989) was not significantly associated with NPC risk. These results were only reported in the text of the paper. In the second of the studies carried out in China,

16

the households of NPC cases were significantly less likely to often eat bread compared to the households of the controls (OR 0.43; 95% CL 0.27, 0.70) (Geser et al., 1978). The third study investigated Chinese living in Malaysia. In this study, cases were significantly more likely than controls to consume bread for breakfast, but further details were not reported (Armstrong, 1978). Interpreting the results of these three studies, which were very inconsistent, is hindered by the lack of detailed information. The inconsistent overall results could be a consequence of the heterogeneity in the exposures and study design features, or to fluctuation around an overall null result. Bread: Childhood consumption A3 Case-control studies (3) Three case-control studies reported on childhood bread consumption in relation to NPC risk. Two of these studies were carried out by Yu and colleagues in China. For these, the exposure measured was bread consumption at ten years of age. In results that were adjusted for at least age and sex, Yu and colleagues observed that bread consumption at age 10 years (Yu et al., 1989, Yu et al., 1988) was not significantly associated with NPC risk, as reported in the text of these papers. In contrast to these studies, the other study on this topic was conducted in Algeria and the exposure investigated was chewing bread crust during teething. In this study, the odds of chewing the crust of bread when teething were identical in NPC cases and controls (Laouamri et al., 2001). Overall, this evidence is consistent in suggesting that bread consumption during childhood is not associated with NPC. Noodles A3 Case-control studies (1) A study of Chinese in Malaysia compared 60 NPC cases to 150 controls with respect to the extent that the families of study participants ate noodles during meals. In matched analyses, the overall matched odds ratio of 1.2 indicates that families of cases were slightly more likely than the families of controls to eat noodles with their meals (Armstrong, 1978). In analyses by ethnic group, a stronger, statistically significant association was observed in the combined Hokkien plus Teochiu group. Rice A3 Case-control studies (2) Two studies reported on the association between eating rice and risk of NPC. A study of Chinese in Malaysia reported on the following associations: family eats rice for breakfast, family eats plain rice during evening meals, and family eats rice porridge during evening meal (Armstrong, 1978). Patterns of familial rice consumption were described in the text with very little detail. This study compared 60 NPC cases to 150 controls. A study carried out in China compared 104 NPC cases with 104 controls. In results that were unadjusted, eating rice at age 10 was inversely associated with risk of NPC (OR 0.71; 95% CI 0.51-0.92) (Huang, 1997). A5 Ecological studies (1) One study examined the per capita consumption of rice as determined in a food survey in both sexes of Chinese living in Hong Kong. The age-adjusted rates of NPC were significantly positively correlated with consumption of rice in both males and females (Koo et al., 1997). 2.1.2 Starchy roots, tubers and plantains A3 Case-control studies (2)

17

Two case-control studies examined the risk of NPC in association with consumption of starchy root vegetables. In one study, conducted in Algeria, the specific dietary exposure investigated was consumption of mashed potatoes during childhood. The results of this study showed a non-significantly elevated odds ratio of 2.0 (CI 0.06 – 59.7) for eating mashed potatoes >7 times versus <3 times per week, after adjustment for age, gender and residence area (Laouamri et al., 2001). The second case-control study was conducted by a team of investigators in China using a questionnaire to measure taro and sweet potato consumption in 101 cases and 199 controls. The investigators reported a lower risk of NPC with high versus no consumption of taro (OR 0.76; 95% CI 0.46 – 1.26) and sweet potatoes (OR 0.67; 95% CI 0.33 – 1.36) unadjusted for other factors (Zou, 1999). No trend was reported. 2.1.3 Other starchy foods No results found. 2.2 Fruit and (non-starchy) vegetables A3 Case-control studies (1) One case control study conducted in Tunisia examined the association of NPC with combined fruits and vegetables. Two controls were matched by age, sex, and area of residence to each case resulting in 80 included cases and 160 controls. They reported only that the data indicated no significant association between NPC risk and fruits and vegetables (Jeannel et al., 1990a). 2.2.1 Non-starchy vegetables Total non-preserved vegetables: Adulthood consumption A3 Case-control studies (5) A total of 5 case-control studies reported results for total non-preserved vegetables and NPC; however, only 2 provided enough information for a dose-response meta-analysis. All five studies were conducted in China and matched cases and controls. Four studies were included in a highest-versus-lowest forest plot and reported associations in the protective direction. The first study by Ward et al observed a highest-versus-lowest odds ratio of 0.6 (95% CI: 0.4-1.0) for vegetable intake after adjusting for age, sex, ethnicity/race, subjects with mother’s questionnaire, and total caloric intake (Ward et al., 2000). Yuan et al reported a maximally adjusted odds ratio of 0.85 (95% CI: 0.65-1.10) when comparing intake more than 2.4 times a day to intake less than 1.5 times per day (Yuan et al., 2000b). A study of 135 cases and 135 controls observed a significant association between non-starchy vegetables and NPC (OR=0.51, 95% CI: 0.29-0.88) when comparing intake more than 15.75 times per month to intake less than 15.75 times per month (Ye, 1995). The fourth study by Wang et al reported a maximally adjusted highest-versus-lowest OR of 0.256 (p=0.0051) (Wang, 1993). The fifth study, which was not included in the highest-versus-lowest forest plot, only reported a non-significant association between consumption of fresh vegetables 3 years prior to diagnosis and NPC (Ning et al., 1990).

Forest Plot for Highest vs. Lowest Analysis: Total non-starchy vegetables, Case-control studies

18

Odds Ratio: Highest vs. Lowest intake

.025 1 1.5

Study

Effect size

(95% CI)

NAS00531 (Ward, 2000) 0.60 ( 0.38, 0.95)

NAS00577 (Yuan, 2000) 0.85 ( 0.65, 1.11)

NAS06003 (Ye, 1995) 0.51 ( 0.29, 0.89)

NAS06022 (Wang, 1993) 0.26 ( 0.10, 0.67)

A5 Ecological studies (2) Two ecological studies examined the risk of NPC related to consumption of vegetables in Chinese residents in Hong Kong and China. The study in Hong Kong used per capita consumption to identify exposures and indicated significant correlations between the consumption of fresh vegetables and NPC after adjusting for age (r2=-0.77, p=0.009 among men and r2=-0.75, p=0.013 among women) (Koo et al., 1997). The second study determined local area consumption by interviews with residents and showed an increasing risk of NPC with increases in local consumption of non-starchy vegetables (r2=2.36) (Guo, 2001). This study did not report any adjustments for potential confounding variables or any report on whether the finding was significant. Total non-preserved vegetables: Childhood/Infancy consumption A3 Case-control studies (2) Two studies reported on consumption of non-preserved vegetables early in life. In a case-control study in China, evidence of a protective association (OR 0.3 to 0.6) was observed for eating fresh non-preserved vegetables at age 10, at age 3, and during weaning, and for mother’s consumption during breastfeeding (Ward et al., 2000). The results of another Chinese study of intake at age 10 observed no significant association between fresh vegetable consumption and NPC (Ning et al., 1990). Green vegetables: Adulthood consumption A3 Case-control studies (4) The four case-control studies reporting on green vegetable consumption were included in a highest-versus-lowest forest plot. The first study was conducted in the United States and included 129 cases and 206 controls (Farrow et al., 1998). They reported a highest-versus-lowest odds ratio of 0.99 (95% CI: 0.51-1.94) for the intake of labeled dark green vegetables. The second study of Chinese in Malaysia reported an odds ratio of 0.50 (95% CI: 0.23-1.07) for more than weekly consumption of green vegetables 5 years prior to diagnosis compared to monthly consumption (Armstrong et al., 1998b). In the third study, which matched 104 cases and 104 controls from China, a logistic regression OR of 0.63 (95% CI: 0.44-0.91) was observed for consumption of green peppers, chives, and celery (Chen et al., 1997). The fourth study, also from China, reported a highest-versus-lowest OR of 0.63 (95% CI 0.44-0.91) for green peppers, chives, and celery when consumed 3 years prior to diagnosis (Huang, 1997).

19

Forest Plot for Highest vs. Lowest Analysis: Green vegetables, Case-control studies


.075 1 2

Study

Effect size

(95% CI)

NAS00700 (Farrow, 1998) 0.99 ( 0.51, 1.93)

NAS00749 (Armstrong, 1998) 0.50 ( 0.23, 1.08)

NAS00825 (Chen, 1997) 0.63 ( 0.44, 0.91)

NAS06024 (Huang, 1997) 0.63 ( 0.44, 0.91)

Green vegetables: Childhood consumption A3 Case-control studies (3) Three case-control studies investigated the association between childhood consumption of green vegetables and NPC. A study of Chinese in Malaysia reported an odds ratio of 0.59 (95% CI: 0.33-1.06) for more than weekly consumption of green vegetables at age 10 compared to monthly consumption (Armstrong et al., 1998b). In the second study, which matched 104 cases and 104 controls from China, a logistic regression OR of 0.54 (95% CI: 0.38-0.78) was observed for consumption of green peppers, chives, and celery at age 10 (Chen et al., 1997). The third study, also from China, reported results for fresh green vegetable consumption during multiple childhood stages (Yu et al., 1989). A protective, yet non-significant, association was observed for consumption during weaning (OR=0.6, 95% CI: 0.3-1.1). Non-significant results in the direction of risk were reported for intake during ages 1-2 (OR=1.7, 95% CI: 0.6-4.9) and at age 10 (OR=1.3, 95% CI: 0.3-5.1). Other non-preserved vegetables A3 Case-control studies (2) A study of Chinese in Malaysia evaluated intakes of vegetables at different meals and the risk of NPC (Armstrong, 1978). A significant odds ratio of less than one was reported for vegetables eaten at breakfast and for fresh vegetables eaten at evening meals among families of participants. Among cases and controls, an odds ratio of 0.9 was reported for vegetables eaten at three main daily meals when adjusted for age, sex, census district, household type, race and ethnicity, and socioeconomic status. In a study of Chinese in China, frequent consumption of coloured vegetables was significantly associated with NPC risk when compared to less frequent consumption after adjustment for various cofounders (OR=0.111, p=0.0108) (Wang, 1993). Total preserved vegetables: Adulthood consumption A3 Case-control studies (7) A total of 7 case-control studies reported results for total preserved vegetables and NPC; however, only 2 provided enough information for a dose-response or highest-versus-lowest meta-analysis. Ever-versus-never

20

consumption of preserved vegetables was not significant in a Chinese study of 375 cases and 327 controls (Ward et al., 2000). A large Chinese study of 935 cases and 1032 controls by Yuan et al observed a significant association between preserved vegetable intake and NPC (OR=1.43, 95% CI: 1.11-1.86) (Yuan et al., 2000b). Lee et al also reported a significant association between canned, salted, or pickled vegetables and NPC (OR=4.9, CI: 1.8-12.9) (Lee et al., 1994). Two studies by Zheng et al, one published in 1993 and one in 1994, reported different results for preserved vegetables (Zheng et al., 1993, Zheng et al., 1994b). The first reported a significant risk association for salted vegetables and the second reported no significant association for salted, dried, or tinned vegetables in brine. In a study of 100 cases and 300 matched controls conducted in China, no significant associations were reported for dried, salted, or pickled vegetables (Ning et al., 1990). The final study included 100 cases and 100 controls in China and observed a significant regression slope of 0.015 for the intake of pickled vegetables after adjusting for environmental factors, gas range, pungent foods, and socio-economic status (Duan, 2000). Total preserved vegetables: Childhood/Infancy consumption A3 Case-control studies (4) Four case-control studies investigated preserved vegetables during childhood and risk of NPC. The first study by Ward et al matched cases and controls in China (Ward et al., 2000). Non-significant associations were reported for intake of preserved vegetables at age 10 (OR=0.9, 95% CI: 0.3-2.6), at age 3 (OR=0.9, 95% CI: 0.3-2.4), and during weaning (OR=1.3, 95% CI: 0.6-2.5). Consumption of canned, salted or pickled vegetables at age 10 was not observed to be associated with NPC (OR=0.5, 95% CI: 0.1-1.4) in a study of Chinese in Singapore (Lee et al., 1994). A study by Jeannel et al reported an adjusted odds ratio of 2.2 for consumption of pickled vegetables during weaning, but no other details were offered (Jeannel et al., 1990a). Ning et al observed no significant associations for dried, salted, or pickled vegetables at age 10 (Ning et al., 1990). 2.2.1.1 Non-starchy root vegetables and tubers Total Root Vegetables A3 Case-control studies (1) One case-control study evaluated the association between total non-starchy root vegetables and tubers. The study conducted in Algeria included 72 cases and 72 controls (Laouamri et al., 2001). With adjustment for age, sex, and area of residence, a non-significant odds ratio of 1.0 was reported for use of non-starchy root vegetables and tubers when teething and NPC risk. Carrots: Adulthood consumption A3 Case-control studies (2) Two case-control studies evaluated the association between carrot consumption during adulthood and NPC. Adult consumption of carrots (within the past three to five years) was reported in the text as being not statistically significant in one study (Chen et al., 1997) and in another an odds ratio of 0.8 (95% CL 0.3, 1.9) was reported (Ning et al., 1990). Both studies were conducted in China and adjusted for age, sex, and area of residence. Carrots: Childhood consumption A3 Case-control studies (6) Four of the six case-control studies investigating consumption of carrots during childhood were included in a highest-versus-lowest analysis. A formal meta-analysis of these studies was not deemed tenable because two of

21

the six studies only reported findings in the text as being “not statistically significant”, and of the remaining studies there was heterogeneity in the exposure window studied, varying from baby food (Laouamri et al., 2001) to age 10 years (Chen et al., 1997, Huang, 1997, Yu et al., 1989). In a study in Algeria, consumption of carrots as a baby food was inversely associated with NPC (OR=0.3, 95% CI: 0.1-0.87) (Laouamri et al., 2001). At age 10 years, odds ratios in the protective direction were observed in three Chinese studies (Huang, 1997, Ning et al., 1990, Yu et al., 1989). Yu et al and Huang et al reported significant odds ratios of 0.2 (95% CI: 0.1-0.3) and 0.6 (95% CI: 0.41-0.99), respectively. Ning et al observed a non-significant odds ratio of 0.4 (p=0.09) when adjusting for age, sex, area of residence, salted fish and salted shrimp paste consumption at age 10. The two remaining studies not included in the highest-versus-lowest plot reported non-significant results for carrot consumption at age 10 (Chen et al., 1997, Yu et al., 1989).

Forest Plot for Highest vs. Lowest Analysis: Carrots, Case-control studies


.025 1 1.5

Study

Effect size

(95% CI)

NAS00424 (Laouamri, 2001) 0.30 ( 0.10, 0.89)

NAS01459 (Yu, 1989) 0.20 ( 0.12, 0.35)

NAS01922 (Ning, 1990) 0.40 ( 0.14, 1.15)

NAS06024 (Huang, 1997) 0.60 ( 0.39, 0.93)

Preserved Root Vegetables A3 Case-control studies (2) The association between preserved root vegetables and NPC was evaluated in two case-control studies. Salted root vegetables were reported to be significantly associated with NPC among 97 cases and 192 controls in China (unadjusted OR=2.2; 95% CL: 1.3-2.2) (Zou, 1999). In another Chinese study, pickled root vegetables consumed at age 10 were inversely associated with NPC (OR=0.75, 95% CI: 0.57-0.99), preserved root vegetables consumed at age 10 were positively associated with NPC (OR=1.81, 95% CI: 1.01-3.33), and other preserved root vegetables consumed during adulthood were positively associated with NPC (OR=2.42, 95% CI: 0.99-5.92) (Huang, 1997). 2.2.1.2 Cruciferous vegetables Cabbage: Adulthood consumption A3 Case-control studies (3)

22

Three studies, all conducted in China, evaluated the relationship between cabbage consumption and NPC in China. In a large study of 935 cases and 1032 controls, no association was reported for daily intake and NPC when compared to less than weekly intake (OR=0.97, 95% CI: 0.81-1.17) of fresh bok choi (Chinese white cabbage) (Yuan et al., 2000b). Using a maximally adjusted model, Armstrong et al observed a significant protective association for more than monthly consumption of Chinese flowering cabbage (OR=0.5, p=0.0004) in a study of 282 cases and 282 matched controls (Armstrong et al., 1998b). Huang et al also reported a significant protective association for cabbage intake 3 years prior to diagnosis (OR=0.628, 95% CI: 0.44, 0.90) among 104 cases and 104 controls (Huang, 1997). Non-Preserved Cruciferous Vegetables: Adulthood consumption A3 Case-control studies (5) Five case-control studies assessed the relationships between various cruciferous vegetables and NPC, only one observed a significant association. Chinese kale was reported as protective, but not significant, when consumed more than weekly among matched cases and controls from China (OR=0.63, 95% CI: 0.39-1.01) (Armstrong et al., 1998b). Chen et al reported a significant logistic regression odds ratio of 0.63 (95% CI: 0.44-0.90) for intake of Chinese cabbage and rutabaga (Chen et al., 1997). In a study of Chinese in Singapore, turnip root was not observed to be associated with NPC when consumed more than 3 times per month (OR=1.0, 95% CI: 0.1-5.6) (Lee et al., 1994). No association was reported between mustard consumption and NPC by Ning et al in a study 100 cases and 300 controls matched for age, sex, and area of residence (Ning et al., 1990). Huang et al examined the association between cauliflower intake and NPC, but observed no significance (OR=1.048, 95% CI: 0.36-3.05) (Huang, 1997). Non-Preserved Cruciferous Vegetables: Childhood consumption A3 Case-control studies (6) Six case-control studies assessed the relationships between various cruciferous vegetables consumed during childhood and NPC. Chinese flowering vegetable consumed at age 10 was reported to be significantly protective (OR=0.47, 0.29-0.77) in a study by Armstrong et al, but Chinese kale consumed at the same age was not (OR=0.71, 0.40-1.27) (Armstrong et al., 1998b). Chen et al reported no association between Chinese cabbage and rutabaga consumption at age 10 and NPC in a matched case-control study conducted in China (Chen et al., 1997). Consumption of turnip root was not observed to be related to NPC in a study of Chinese in Singapore (OR=1.2, 95% CI: 0.4-3.4) (Lee et al., 1994). Mustard, consumed at age 10, was not associated with NPC in a matched case-control study in China (Ning et al., 1990); however, significant results were observed for leaf mustard consumed around 1978 (OR=1.92, 95% CI: 1.46-2.53) and 1968 (OR=1.44, 95% CI: 1.56-1.80) in another Chinese study (Cai, 1996). In the sixth study, cauliflower consumption at age 10 was reported to be protective with an odds ratio of 0.70 (95% CI: 00.52-0.94) among matched cases and controls in China (Huang, 1997). Preserved Cruciferous Vegetables: Adulthood consumption A3 Case-control studies (5) Of the five studies that reported results for preserved cruciferous vegetables consumed during adulthood, only 2 presented odds ratios. All 5 studies included Chinese men and women from Singapore or China. The first study by Chen et al observed no significant association between pickled Chinese cabbage and NPC (Chen et al., 1997). In the second study by Lee et al, results for 3 types of preserved cruciferous vegetables were in the risk direction, but only 2 were significant (Lee et al., 1994). The 2 significant results were for preserved Chinese radish (OR=2.8, 95% CI: 1.2-6.0) and salted mustard greens (OR=3.1, 95% CI: 1.4-6.5). No significance was observed for preserved cabbage (OR=1.5, 95% CI: 0.6-3.4). Yu et al and Ning et al both reported no significant

23

association for salted mustard greens and sour cabbage, respectively (Ning et al., 1990, Yu et al., 1986). In the fifth study, both pickled leaf mustard (OR=6.11, p<0.01) and pickled radish (OR=1.75, 95% CI: 1.10-2.79) were observed to be significantly related to NPC (Ye, 1995). Preserved Cruciferous Vegetables: Childhood consumption A3 Case-control studies (4) Four studies focused on various preserved cruciferous vegetables and any age group below age 10 years, with 3 reporting estimates for odds ratios. All four studies assessed the association between types of preserved cabbage at age 10 and NPC. Chen et al reported a protective odds ratio of 0.75 (95% CI: 0.57-0.99) for pickled cabbage consumption at age 10, whereas Yu et al (1988) observed no significant association (Chen et al., 1997, Yu et al., 1988). No significance was observed for preserved cabbage consumption at age 10 by Lee et al (OR=0.8, 95% CI: 0.2-2.6); for salted cabbage at age 10 by Yu et al (1988); or for sour cabbage at age 10 by Ning et al (Ning et al., 1990). Preserved radish was examined in two of the studies. In the first study of Chinese in Singapore (Lee et al., 1994), an odds ratio of unity (95% CI: 0.4-2.1) was reported for consumption of preserved Chinese radish at age 10. The second study from China (Yu et al., 1988) observed no significant association between the consumption of salted radish at age 10 and NPC. Two studies (Lee et al., 1994, Yu et al., 1988) examining the risk of salted mustard greens at age 10 showed no association. Yu et al (1988) also assessed consumption at ages 1-2 and weaning. No association was observed at ages 1-2, but salted mustard greens consumed during weaning were reported to be in the risk direction (OR=5.4, 95% CI: 1.2-23.8) in an ever-versus-never analysis. 2.2.1.3 Allium vegetables A3 Case-control studies (1) In a case-control study of Chinese in China, the association between NPC and consumption of garlic at age 10 or in adulthood was investigated using a food frequency questionnaire. There were 100 NPC cases and 300 controls. The authors reported no significant associations after adjustments were made for age, gender and area of residence (Ning et al., 1990). 2.2.1.4 Green leafy vegetables (not including cruciferous vegetables) Total Green Leafy Vegetables: Adulthood consumption A3 Case-control studies (4) Four studies, all from China, examined the association between adulthood consumption of green leafy vegetables and NPC. Two of the studies observed significant protective associations, whereas the other two studies observed risk associations, one significant and one not significant. Yuan et al reported a non-significant maximally adjusted odds ratio of 1.25 (95% CI: 0.73-2.14) for fresh dark green leafy vegetables (Yuan et al., 2000b). Zheng et al and Ye et al both used matched cases and controls and observed significant protective associations for leafy vegetables (OR=0.1, p=0.008 and OR=0.29, p<0.01, respectively) (Ye, 1995, Zheng et al., 1994b). In a study by Huang et al, a significant risk association was observed for green leafy vegetables consumed 3 years prior to diagnosis (OR=1.733, 95% CI: 1.19-2.53) (Huang, 1997).

Forest Plot for Highest vs. Lowest Analysis: Green leafy vegetables, Case-control studies

24


.005 1 3

Study

Effect size

(95% CI)

NAS00577 (Yuan, 2000) 1.25 ( 0.73, 2.14)

NAS01113 (Zheng, 1994) 0.10 ( 0.02, 0.55)

NAS06003 (Ye, 1995) 0.29 ( 0.11, 0.74)

NAS06024 (Huang, 1997) 1.73 ( 1.19, 2.52)

Total Green Leafy Vegetables: Childhood consumption A3 Case-control studies (2) Two case-control studies from China studied the association between green leafy vegetables and NPC. The first study of 128 cases and 174 controls reported non-significant associations for fresh green leafy vegetables when consumed during weaning (p-for-trend 0.86), between ages 1-2 (p-for-trend 0.92), and at age 10 (Yu et al., 1988). In the second study, 115 cases and 115 controls were recruited from area hospitals during the 1991 calendar year (Cai, 1996). An adjusted odds ratio of 0.514 (95% CI: 0.34-0.78) was reported for green leafy vegetables consumed around 1968 and 0.444 (95% CI: 0.29-0.67) for consumption around 1978. Water spinach A3 Case-control studies (1) A study of Chinese in Malaysia including 282 cases and 282 controls investigated the association between consumption of water spinach at age 10 and 5 years prior to diagnosis and risk of NPC (Armstrong et al., 1998b). An unadjusted odds ratio of 0.72 (95% CI 0.45-1.17) was reported for those who consumed water spinach more than weekly 5 years prior to diagnosis compared to those with monthly consumption. More than weekly consumption at age 10 was reported as being significantly associated with NPC when compared to monthly consumption (unadjusted OR=0.51, 95% CI 0.28-0.93). Preserved Green Leafy Vegetables: Adulthood consumption A3 Case-control studies (3) Three case-control studies evaluated the association between preserved green leafy vegetables and NPC. The first study of Chinese in Malaysia reported an unadjusted odds ratio of 3.33 (95% CI: 1.84-6.01) when comparing more than weekly intake of salted green leafy vegetables to monthly consumption (Armstrong et al., 1998b). A second study of Chinese in Singapore reported a non-significant association between mei chye (preserved greens and leafy vegetables) and NPC after adjusted for various confounders (Lee et al., 1994). The third study of Chinese in China reported non-significant associations between dried kelp and dried seaweed and NPC after adjusting for age, sex, and area of residence (Ning et al., 1990).

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Preserved Green Leafy Vegetables: Childhood consumption A3 Case-control studies (2) Two case-control studies evaluated the association between preserved green leafy vegetables consumed during childhood and NPC. The first study of Chinese in Malaysia reported an unadjusted odds ratio of 0.84 (95% CI: 0.45-1.58) when comparing more than weekly intake of salted green leafy vegetables at age 10 to monthly consumption (Armstrong et al., 1998b). The second study of Chinese in China reported non-significant associations between consumption of dried kelp at age 10 and consumption of dried seaweed at age 10 and NPC after adjusting for age, sex, and area of residence (Ning et al., 1990). 2.2.1.5 Other non-starchy vegetables Tomatoes: Adulthood consumption A3 Case-control studies (5) Five studies evaluated the relationship between tomato consumption during adulthood and NPC, with four providing enough information for a highest-versus-lowest analysis. Of the four studies, 2 showed significant protective associations, and 2 reported non-significant results. No association was assessed for daily intake in a large Chinese study of 935 cases and 1032 controls when maximally adjusted (OR=0.92, p-for-trend=0.10) (Yuan et al., 2000b). In a study of Chinese in Malaysia, more than weekly intake 5 years prior to diagnosis was significantly associated with NPC risk (OR=0.5, 95% CI: 0.28-0.87) (Armstrong et al., 1998b). Zou et al reported an odds ratio in the direction of risk for intake nine times or more a month, but the confidence interval was wide and therefore not significant (OR=2.59, 95% CI: 0.69-9.72) (Zou, 1999). The study by Huang et al was the second study to report a significant protective association for tomato consumption (Huang, 2002). They observed an odds ratio of 0.57 (95% CI: 0.39-0.83) for frequent consumption compared to less frequent consumption among matched cases and controls. The fifth study, which was not eligible for highest-versus-lowest analysis, reported a significant association for tomatoes, but failed to provide any other details (Yu et al., 1989).

Forest Plot for Highest vs. Lowest Analysis: Tomatoes, Case-control studies


.05 1 10

Study

Effect size

(95% CI)

NAS00577 (Yuan, 2000) 0.92 ( 0.83, 1.01)

NAS00749 (Armstrong, 1998) 0.50 ( 0.28, 0.88)

NAS06023 (Zou, 1999) 2.59 ( 0.69, 9.72)

NAS06030 (Huang, 2002) 0.57 ( 0.39, 0.83)

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Tomatoes: Childhood consumption A3 Case-control studies (3) The association between childhood tomato consumption and NPC was assessed in three case-control studies. In the first study of Chinese in Malaysia, an odds ratio of 0.80 (95% CI: 0.48-1.32) was reported for more than weekly intake compared to monthly intake of tomatoes (Armstrong et al., 1998b). In a Chinese study including matched cases and controls, strong protective trends were observed for tomato consumption at age 10 (OR=0.3, p-for-trend<0.05), at ages 1-2 (OR=0.3, p-for-trend<0.05), and during weaning (OR=0.0, 95% CI: 0.0-0.9) (Yu et al., 1989). In the third study, which matched cases and controls from China, no significant associations were reported for consumption at age 10 or at ages 1-2 (Yu et al., 1988). Other Non-Preserved Vegetables: Adulthood consumption A3 Case-control studies (3) Three studies examined various non-preserved vegetables consumed during adulthood and NPC. The first study included 935 cases and 1032 controls from China and used a food frequency questionnaire to assess intake (Yuan et al., 2000b). Daily intakes of fresh light green/orange leafy vegetables (OR=0.98, 95% CI: 0.63-1.50), fresh gourds (OR=0.89, 95% CI: 0.73-1.09), and fresh green peppers (OR=0.67, p=0.43) were not shown to be associated with NPC when compared to less than weekly intake and adjusted for various confounders. Significant protective trends were observed for the consumption of sliced raw chilli at evening meals and at 3 main daily meals in a study of Chinese in Malaysia (Armstrong, 1978). In a Chinese study of 135 cases and 135 controls matched by age, sex, and area of residence (Ye, 1995), white coloured vegetables were observed to be protective when consumed more than 3.3 times a month (OR=0.30, 95% CI: 0.18-0.51). Other Non-Preserved Vegetables: Childhood consumption A3 Case-control studies (2) Two studies reporting results for other non-preserved vegetables consumed during childhood showed significant protective associations. Both studies were conducted in China and matched cases and controls by age, sex, and area of residence. Cai et al observed significant relationships for yellow coloured vegetables consumed around 1968 (OR=0.64, 95% CI: 0.45-0.91) and 1978 (OR=0.83, 95% CI: 0.44-0.91) (Cai, 1996). An ever-versus-never odds ratio of 0.55 (95% CI: 0.33-0.92) was reported for green bean and eggplant consumption at age 10 in a study by Huang et al (Huang, 1997). Total Preserved Vegetables: Adulthood consumption A3 Case-control studies (5) Of the 5 studies reporting results for total preserved vegetables consumed during adulthood, 4 provided adequate details to be included in a highest-versus-lowest analysis. In an Algerian study, 72 cases and 72 controls were matched by age, sex, and area of residence (Laouamri et al., 2001). This study observed vegetables in brine used as seasonings to be significantly related to NPC (OR=2.77, 95% CI: 1.34-5.71). A Chinese study by Yuan et al examined various types of preserved vegetables in a population of 935 cases and 1032 controls (Yuan et al., 2000b). They reported a significant risk for the consumption of preserved stem vegetables (OR=1.88, 95% CI: 1.24-2.84) and non-significant associations in the direction of risk for the consumption of preserved leafy vegetables (OR=1.37, 95% CI: 0.65-2.9) and preserved root vegetables (OR=1.04, 95% CI: 0.7-1.53). Mei chye, a dish of preserved greens and leafy vegetables, was shown to be in the direction of risk, but not significant (OR=2.8, 95% CI: 0.9-8.2) in a study of Chinese in Singapore (Lee et al., 1994). Zou et al observed a significant risk association for salted non-starchy vegetables when consumed more than 9 times a month (OR=2.28, 95% CI: 1.40-3.73) in a study of 100 cases and 202 controls in China

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(Zou, 1999). The fifth study, which was not eligible for inclusion in the meta-analysis, reported no significant association between salted vegetables and NPC (Chen et al., 1997).

Forest Plot for Highest vs. Lowest Analysis: Total preserved vegetables, Case-control studies


.25 1 9

Study

Effect size

(95% CI)

NAS00424 (Laouamri, 2001) 2.77 ( 1.34, 5.72)

NAS00577 (Yuan, 2000) 1.37 ( 0.65, 2.90)

NAS01056 (Lee, 1994) 2.80 ( 0.93, 8.46)

NAS06023 (Zou, 1999) 2.28 ( 1.40, 3.72)

Total Preserved Vegetables: Childhood consumption A3 Case-control studies (3) Three studies reported on preserved vegetables consumed during childhood; 2 reported significant protective associations for intake of salted vegetables at age 10. In the first study to examine salted vegetables, 104 cases and 104 controls were matched by age, sex, and area of residence and a logistic regression odds ratio of 0.76 (95% CI: 0.58-0.99) was observed (Chen et al., 1997). The second study reported similar results (OR=0.755, 95% CI: 0.58-1.0) for salted vegetables (Huang, 1997). In a study of Chinese in Singapore (Lee et al., 1994), including 150 cases and 341 controls, intake of preserved greens and leafy vegetables was not significantly associated with NPC (OR=1.3, 95% CI: 0.6-2.6) when adjusting for age, sex, education level, and dialect group. Other Preserved Vegetables: Adulthood consumption A3 Case-control studies (5) A heterogeneous mix of preserved vegetables consumed during adulthood was investigated in 5 case-control studies, all reported significant risk associations with NPC. An odds ratio of 7.5 (95% CI: 3.09-18.2) was reported for salted and dried tomatoes in an Algerian study which matched 72 cases and 72 controls by age, sex, and area of residence (Laouamri et al., 2001). Armstrong et al observed more than weekly consumption of salted root to be a risk factor for NPC (OR=2.19, 95% CI: 1.33-3.62) in study of Chinese in Malaysia (Armstrong et al., 1998b). Plum vegetable was shown as significantly associated with NPC (OR=2.53, 95% CI: 1.04-6.19) when maximally adjusted for in a Chinese study (Chen et al., 1997). After adjusting for age, sex, education level, and dialect group, salted Chinese tuber consumption was significantly associated with NPC (OR=2.4, 95% CI: 1.1-5.2) in a study of Chinese in Singapore (Lee et al., 1994). An ever-versus-never odds ratio of 3.3 (p=0.03) was observed for pickled vegetables with fungus after adjusting for age, sex, area of residence, and living condition score in a Tunisian study of 80 cases and 160 controls (Jeannel et al., 1990a).

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Other Preserved Vegetables: Childhood consumption A3 Case-control studies (4) In several studies, associations in the direction of increased risk were observed relating salted/preserved vegetable intake during childhood and NPC (Armstrong et al., 1998b, Jeannel et al., 1990a, Lee et al., 1994). Salted root intake at age 10 was in the risk direction, but not significant in 2 studies. The first study of Chinese in Malaysia included 282 cases and 282 controls (Armstrong, 1998) and observed an odds ratio f 1.75 (95% CI: 0.98-3.10) for more than weekly consumption compared to monthly consumption. The second study to examine salted root included 128 cases and 174 controls from China (Yu et al., 1988) and reported an age and sex adjusted odds ratio of 3.2 (95% CI: 0.6-17.6) for daily consumption compared to rare intake. In the same study by Yu et al, a significant association was observed for chung choi consumption during weaning using a maximally adjusted model (OR=0.518, p=0.042). Sze chuan chye, a salted Chinese tuber, was not found to be associated with NPC (OR=1.4, 95% CI: 0.4-4.5) in a study of Chinese in Singapore which included 145 cases and 340 controls (Lee et al., 1994). Jeannel et al (1990) reported a significant risk association for pickled vegetables with fungus consumed during weaning (OR=3.8, p=0.03) in a study of Tunisian cases and controls. 2.2.1.6 Raw vegetables A3 Case-control studies (2) Two case-control studies conducted by Armstrong and colleagues among Chinese in Malaysia reported on the associations between consumption of raw foods and NPC. Statistically significant trends in the protective direction were observed with greater consumption of raw green vegetables (p-for-trend 0.026) (Armstrong et al., 1998b) and sliced raw chilli (cases ate less at evening meals) (Armstrong, 1978). 2.2.2 Fruits Total non-preserved fruits: Adulthood consumption A3 Case-control studies (6) The evidence for non-preserved fruits consumed during adulthood was not amenable to meta-analysis since only 3 case-control studies provided sufficient information to be included. Of the six studies, 4 specified the intake of fresh fruits (Armstrong, 1978, Huang, 2002, Ning et al., 1990, Zheng et al., 1994a). A protective odds ratio was reported in 4 studies, although only 2 were statistically significant. Zheng et al and Ning et al reported non-significant results for the consumption of fresh fruit using a matched case-control design. Total non-preserved fruits: Childhood consumption A3 Case-control studies (4) In four studies, associations were examined relating non-preserved fruit intake during childhood and NPC. All studies included Chinese cases and controls, one from Taiwan and three from China. The study from Taiwan reported adjusted odds ratios of 0.9 (95% CI-0.3-2.6) for intake at age 3, 2.1 (95% CI: 0.6-7.4) for intake during weaning, and 0.5 (95% CI: 0.2-1.5) for mother’s diet during breastfeeding (Ward et al., 2000). Zheng et al and Ning et al reported non-significant results for fresh fruit consumption at age 10 or at ages 0-3 (Ning et al., 1990, Zheng et al., 1994a). The fourth study examined fresh fruit consumed around 2 different decades and observed significant protective associations for both (OR=0.67, 95% CI: 0.49-0.90 around 1968 and OR=0.68, 95% CI: 0.52-0.89) (Cai, 1996). Preserved fruits

29

A3 Case-control studies (1) A study of Chinese in Malaysia including 282 cases and 282 controls investigated the association between consumption of preserved fruits at age 10 and 5 years prior to diagnosis and risk of NPC (Armstrong et al., 1998b). An unadjusted odds ratio of 1.42 (95% CI 0.71-2.85) was reported for those who consumed preserved fruit more than weekly 5 years prior to diagnosis compared to those with less than monthly consumption. More than weekly consumption at age 10 was not significantly associated with NPC when compared to less than monthly consumption (unadjusted OR=1.50, 95% CI 0.82-2.75). 2.2.2.1 Citrus fruit Total citrus fruit: Adulthood consumption A3 Case-control studies (5) The evidence for citrus fruits was not compatible with the preferred dose-response approach, but analyses using the approach of highest-versus-lowest categories could be implemented with all five case-control studies contributing data. A statistically significant protective association was observed for 4 of the 5 studies, with the fifth study in the protective direction. Yuan et al compared daily intakes of fresh oranges and tangerines to less than weekly intakes and reported a maximally adjusted odds ratio of 0.06 (p-for-trend 0.0005) (Yuan et al., 2000b). In a US study, the only study outside of China, an adjusted odds ratio of 0.68 (95% CI: 0.33-1.41) was observed for consumption of oranges, grapefruits, and orange juice (Farrow et al., 1998). Armstrong et al and Chen et al implemented maximal adjustment models and observed significant protective associations for oranges and tangerines (OR=0.48, p=0.025 and OR=0.66, 95% CI: 0.50-0.89, respectively) (Armstrong et al., 1998b, Chen et al., 1997). An ever-versus-never odds ratio of 0.63 (95% CI: 0.41-0.95) was reported by Huang et al for consumption of citrus fruits 3 years prior to diagnosis among matched cases and controls from Heilongjiang province, China (Huang, 1997).

Forest Plot for Highest vs. Lowest Analysis: Citrus Fruits, Case-control studies


.0025 1 1.5

Study

Effect size

(95% CI)

NAS00577 (Yuan, 2000) 0.06 ( 0.01, 0.29)

NAS00700 (Farrow, 1998) 0.68 ( 0.33, 1.40)

NAS00749 (Armstrong, 1998) 0.48 ( 0.25, 0.92)

NAS00825 (Chen, 1997) 0.66 ( 0.49, 0.88)

NAS06024 (Huang, 1997) 0.63 ( 0.41, 0.96)

Total citrus fruit: Childhood consumption A3 Case-control studies (4)

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Four studies from China examined the association between childhood consumption of citrus fruits and NPC, only 1 observed significant results (Armstrong et al., 1998b, Chen et al., 1997, Yu et al., 1989, Yu et al., 1988). All four studies reported non-significant results for consumption at age 10. Yu et al (1989) observed a significant protective association for consumption at ages 1-2 (OR=0.3, 95% CI: 0.1-0.9); however, a previous study by Yu et al (1988) did not show a significant association (p=0.86). Preserved citrus fruits A3 Case-control studies (1) One study of 104 cases and 104 controls in China evaluated the association between preserved citrus fruits and NPC (Huang, 1997). Consumption of preserved citrus fruits at age 10 was reported as a risk factor for NPC when compared to no consumption (unadjusted OR=2.17, 95% CI 1.12-4.21). After adjustment for age, sex, no separate kitchen, intake of dried vegetables and grapes, and family history of cancer, an odds ratio of 2.95 (95% CI 1.04-8.41) was reported for consumption of preserved oranges when compared to no consumption. 2.2.2.2 Other Fruits Non-preserved fruits: Adulthood consumption A3 Case-control studies (2) Two studies conducted in China investigated the association between non-preserved fruits consumed during adulthood and NPC. The first study of 104 cases and 104 controls matched for age, sex, and area of residence reported logistic regression results for consumption of apples (OR=0.64, 95% CI: 0.46-0.90), bananas (OR=0.59, 95% CI: 0.42-0.82), grapes (OR=0.42, 95% CI: 0.28-0.64), peaches (OR=0.65, 95% CI: 0.46-0.91), and watermelons (OR=1.56, 95% CI: 1.07-2.27) (Chen et al., 1997). The second study reported similar results for apples (OR=0.641, 95% CI=0.46-0.90), bananas (OR=0.587, 95% CI: 0.42-0.82), peaches (OR=0.651, 95% CI: 0.46-0.91), and watermelons (OR=1.559, 95% CI: 1.07-2.27) (Huang, 1997). When using a subset of the study participants based on provincial region, an odds ratio of 0.567 (95% CI: 0.38-0.85) was reported for banana consumption and 0.312 (95% CI: 0.17-0.58) for grape consumption. Preserved plums: Adulthood consumption A3 Case-control studies (4) Various types of preserved plums consumed during adulthood were examined in four case-control studies. All were in Chinese populations from China or Hong Kong. Yuan et al reported no significance for intakes of dried plums or preserved plums in a study of 935 cases and 1032 controls (Yuan et al., 2000b). Using maximally adjusted models, Chen et al reported significant risk results for the consumption of preserved prunes (OR=2.59, 95% CI: 1.04-8.41) and preserved plums (p-for-trend<0.05) in a matched case-control study (Chen et al., 1997). Limiting dietary intake to 3 years prior to diagnosis, Yu et al did not observe significant associations for 2 types of salted plums; however, when lifetime dietary data was used they observed significant associations for both types of salted plums (risk estimates not provided) (Yu et al., 1989). A second study by Yu et al reported non-significant results for preserved plums after adjusting for age, sex, and salted fish intake (Yu et al., 1986). Preserved plums: Childhood consumption A3 Case-control studies (5) Five studies investigated the relationship between consumption of preserved plums at age 10 and NPC risk; however, only 2 provided enough information for a meta-analysis. All five studies were in Chinese populations from China or Hong Kong. Chen et al reported significant risk associations for preserved prunes (OR=2.17,

31

95% CI: 1.12-4.21) and preserved plums (OR=2.10, 95% CI: 1.12-3.91) using logistic regression analyses and matched cases and controls (Chen et al., 1997). Significant risk trends were observed by Yu et al for 2 types of salted plums (p-for-trends 0.01 and 0.03) after adjusting for age, sex, area of residence, and consumption of salted fish during weaning (Yu et al., 1989). Two previous studies by Yu et al did not observe associations for various preserved plums (Yu et al., 1986, Yu et al., 1988). The fifth study included 104 cases and 104 matched controls and reported a significant risk association for ever-versus-never intake of preserved plums at age 10 (OR=2.10, 95% CI: 1.12-3.91) (Huang, 1997). Preserved olives: Adulthood consumption A3 Case-control studies (3) Three case-control studies evaluated the relationship between preserved olives consumed during adulthood and NPC. A study of 72 cases and 72 matched controls in Algeria reported significant associations between consumption of olives in brine (OR=2.0, 95% CI: 1.36-3.72) and dried olives (OR=4.66, 95% CI: 1.51-14.33) and risk of NPC (Laouamri et al., 2001). An adjusted odds ratio of 1.6 (95% CI: 0.3-7.5) was reported for intake of salted black olives more than once a month compared to no intake among 200 cases and 406 controls of Chinese in Singapore (Lee et al., 1994). The third study of 80 cases and 160 controls in Tunisia reported a maximally adjusted odds ratio of 8.7 for consumption of pickled olives in the year preceding diagnosis (Jeannel et al., 1990a). Preserved olives: Childhood consumption A3 Case-control studies (2) Two studies investigated the relationship between consumption of salted olives at age 10 and NPC risk. The first study of Chinese in Singapore reported a significant inverse association between salted black olives eaten more than once a month and NPC (OR=0.3, 95% CI: 0.1-0.9) (Lee et al., 1994). The second study of 128 cases and 174 controls conducted in China reported a non-significant association between salted olive intake at age 10 and NPC when adjusting for age and sex (Yu et al., 1988). Other preserved fruits: Adulthood consumption A3 Case-control studies (3) Three case control studies measured the association between dried fruits consumed during adulthood and NPC. One study of 72 cases and 72 matched controls in Algeria reported an odds ratio of 0.2 (95% CI: 0.08-0.17) for consumption of raisins (Laouamri et al., 2001). Two studies, one conducted in China and the other in Hong Kong, reported non-significant associations between dried red dates and NPC (Yu et al., 1986, Yuan et al., 2000b). Other preserved fruits: Childhood consumption A3 Case-control studies (2) Two case control studies measured the association between dried red dates consumed at age 10 and NPC. One study was conducted in China and included 128 cases and 174 controls (Yu et al., 1988). The other study took place in Hong Kong and included 250 cases and 250 controls (Yu et al., 1986). Both reported non-significant associations between dried red dates and NPC and provided no other details. 2.3 Pulses (legumes) Non-preserved pulses/legumes

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A2 Cohort studies (1) One cohort study reported the association between non-fermented pulses and NPC (Lin, 1997). A significant association (RR=7.2, 95% CI: 1.4-37.5) was observed for intake 6 or more times a week compared to intake less than twice a week when adjusting for age, EBV status, family history of NPC, and nasopharyngitis in the cohort of 9775 Chinese men in Taiwan. Non-preserved pulses/legumes A3 Case-control studies (2) In an Algerian study of 72 cases and 72 controls matched by age, sex, and area of residence, lentils consumed as baby food 3-7 times week was reported as a significant risk factor for NPC (OR=2.25, 95% CI: 1.0-5.0) when compared to consumption less than three times a week (Laouamri et al., 2001). In a second study by Ward et al, the associations between fresh soybean products consumed at various ages and NPC were evaluated among Chinese men and women in Taiwan (Ward et al., 2000). No significant association was reported for consumption during adulthood. At ages 10 and 3, fresh soybean consumption was reported as protective, but was only significant for age 10 (OR=0.4, 95% CI: 0.-1.0 and OR=0.7, 95% CI: .3-1.7, respectively). Neither consumption during weaning (OR=1.1, 95% CI: 0.5-1.2) or mother’s consumption during breastfeeding (OR=0.7, 95% CI: 0.3-1.6) was observed to be associated with NPC. Preserved soy/tofu: Adulthood consumption A3 Case-control studies (8) Eight case-control studies examined risks of NPC associated with exposure to preserved soy/tofu consumption during adulthood; however, only 3 provided enough detail for meta-analysis. The exposures included in this section were homogeneous in that all consisted of tofu/soy products that were not fresh. Most were fermented, but some others were salted, smelly, and moldy tofu/soy products. The studies were comparable in quality and only differed by the useable detailed information provided. None of the studies adequately controlled for other food intake that would allow evaluation of fermentation versus non-preservation of the same foods. Of the 8 studies in adults, 2 showed significant positive associations (Lee et al., 1994, Yuan et al., 2000b) and 1 showed non-significant positive associations (Zou, 1999), when the highest exposure was compared to the lowest. The remaining studies only indicated significant (Yu et al., 1989, Zheng et al., 1993) or non-significant (Ning et al., 1990, Ward et al., 2000, Yu et al., 1986, Yu et al., 1989) associations with NPC in the text without providing details. Preserved soy/tofu: Childhood consumption A3 Case-control studies (6) Six case-control studies examined risks of NPC associated with exposure to preserved soy/tofu consumption during childhood; however, only 3 provided enough detail for meta-analysis. Studies of childhood intake of fermented tofu/soy products in relation to NPC risk (Lee et al., 1994, Ning et al., 1990, Ward et al., 2000, Yu et al., 1988) indicated no significant increased risk for fermented soy/tofu products. In fact, analyses by (Ward et al., 2000) and (Ning et al., 1990) suggested odds ratios below one, but (Yu et al., 1988) suggested significantly increased risks from consumption of fermented soy bean products. Other preserved pulses/legumes A2 Cohort studies (1)

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One cohort study reported the association between fermented pulses and NPC (Lin, 1997). A significant association (RR=12.7, 95% CI: 2.2-72.3) was observed for intake 6 or more times a week compared to intake less than twice a week when adjusting for age, EBV status, family history of NPC, and nasopharyngitis in the cohort of 9775 Chinese men in Taiwan. A3 Case-control studies (3) This exposure consisted of salted black beans, fermented black bean paste, and fermented beans. Salted black beans were not associated with NPC when consumed during adulthood (OR=2.1, 95% CI: 0.8-5.4) or at age 10 (OR=1.0, 95% CI: 0.4-2.3) in a study of Chinese in Singapore (Lee et al., 1994). Yu et al reported a high risk for fermented black bean paste when consumed at ages 1-2 (OR=4.6, 95% CI: 1.8-11.4), but not when consumed at age 10 (OR=1.4, 95% CI: 0.6-3.1) in a study from China (Yu et al., 1988). When consumed more than 9 times a month, fermented beans were reported as a risk factor for NPC (OR=2.1, 95% CI: 1.3-3.4) in another study from China (Zou, 1999). 2.4 Nuts and Seeds Nuts and seeds: Adulthood consumption A3 Case-control studies (3) Three case-control studies reported on the association between adulthood consumption of nuts and seeds and the risk of NPC. One of these only mentioned in the text that the consumption of dried ginko seeds was not statistically significantly associated with NPC (Yuan et al., 2000b). Interpreting and rating this evidence is challenging without further detail. In a study that took place in Hong Kong (Geser et al., 1978), a strong protective association was noted with fennel seed consumption (OR 0.17; 95% CI 0.05-0.59) after adjusting for age and sex. In the same study, xantho-zylon seeds were not associated with NPC risk. In a study carried out in Algeria (Laouamri et al., 2001), a strong protective association was observed for the broad category of nuts and seeds (OR 0.33; p-value <0.05), and was adjusted for age, sex, and neighbourhood. Nuts and seeds: Childhood consumption A3 Case-control studies (2) Two case-control studies reported on the association between childhood consumption of nuts and seeds and the risk of NPC. Both of these studies were conducted in China. In one of these, the evidence presented was limited to mentioning in the text that the consumption of dried ginko seeds at age 10 years was not statistically significantly associated with NPC (Yu et al., 1988). In the other study, conducted in China, melon seed consumption between the ages of two and ten years was associated with increased NPC risk, with an OR of 2.8 (p-value 0.02), after adjusting for age, sex, area of residence, and sociodemographic score (Zheng et al., 1994b). 2.5 Meat, poultry, fish and eggs No results found. 2.5.1 Meat Preserved meat: Adulthood consumption A3 Case-control studies (7) Seven case control studies addressed the question of whether consumption of preserved meats in adults was associated with an increased risk of NPC; only 3 studies included enough information to be included in a meta-

34

analysis. One study was carried out in Algeria (Laouamri et al., 2001) and one in India (Chelleng et al., 2000) but the remaining five studies were conducted on Chinese populations in China (3), Singapore (Lee et al., 1994) or Taiwan (Ward et al., 2000). Two studies included children and teens in the age range of the subjects but others did not specify and none analyzed the data separately for children. With the exception of the studies of Zheng et al and Ning et al in China, all authors at least adjusted for age and sex in the analysis. All studies included only two categories or did not specify the categories with the exception of the study of Yuan et al in China that had three categories. Therefore, only that study was able to conduct a trend analysis to assess the presence of a possible dose response. All studies used a food frequency questionnaire that was study specific except for the Ward et al study in Taiwanese that used a dietary history questionnaire and the Chelleng et al study in India that did not specify the type of instrument used to assess food intake. The cases included in each of the studies ranged from 47 to 935. The types of exposures to specific preserved meats and the exposure periods varied for each study. Three of the studies found no significant association between consumption of any of the preserved meat products and occurrence of NPC. Ward et al found no significant risk associated with consumption of either cured or smoked meats adjusted for age, sex, and ethnicity when comparing Taiwanese subjects on a never/ever intake basis. The study of Zheng et al found no significant association between salted, dried and tinned meats as a group and NPC but this study did not specify any details on the exposure range used to test significance, the odds ratio or whether any of the data were adjusted for any potential confounding variables (Zheng et al., 1994b). Ning et al examined consumption of cured, smoked and salted meats separately and found no significant association with these foods and NPC (Ning et al., 1990). However, as in the previous study, the exposure range tested was not specified and there was no information regarding whether any of the analyses were adjusted for possible confounders. Four studies reported significant associations between exposure to preserved meats and NPC. Laouamri et al found a significant odds ratio of 4.75 associating consumption of dried or salted meat currently to 29 years ago after adjusting for age sex and area of residence. The Chelleng et al study of consumption of smoked meats in Indians reported an odds ratio of 10.8 based on a never/ever exposed classification and adjusted for multiple household environmental variables as well as tobacco and alcohol use. Yuan et al evaluated the risk associated with consumption of any preserved meat based on a frequency of consumption divided into 3 categories (Yuan et al., 2000b). The odds ratio was significant but low (1.77) as was the trend based on 935 cases and the data were adjusted for the usual variables as well as environmental factors and history of ear infection. The study of Lee et al evaluated the intake of rou gan and dried meat and found a significant association with NPC although the authors failed to provide any details such as the odds ratio. This is the only study that adjusted for other foods and vitamins as well as age, sex, ethnicity and education. The other foods for which the authors have adjusted may not actually be confounding factors or may be correlated with the dried meat intake. Preserved meat: Childhood consumption A3 Case-control studies (4) Four case control studies addressed risks of NPC from consumption of preserved meat in childhood. All studies included only Chinese subjects except for the study by Jeannel et al which was done in Tunisia (Jeannel et al., 1990a). All studies used food frequency questionnaires to determine exposures except for the Taiwan study that used a dietary history. All studies indicated no significant associations between consumption of preserved meats at various ages in childhood and the risk of NPC adjusted for age and sex and, for the Tunisian study only, area and lifestyle factors as well. The Ward et al study in Taiwanese examined the risks for children exposed according to cured or smoked meats at age 10 years, 3 years and at weaning (Ward et al., 2000). The odds ratios were all between 0.8 and 2.2 using an ever/never exposure range. The study of Lee et al in Singapore indicated no association between exposure to rou gan at age 10 and NPC with an odds ratio of 0.8 and a

35

borderline significant negative trend (p=0.08) using exposures at various frequencies per week and never consumed (Lee et al., 1994). The study by Ning et al examined exposures to cured, smoked or salted meats at age 10 and salted meats three years before cancer diagnosis and indicated non-significant associations for all measures without any further details (Ning et al., 1990). 2.5.1.1 Fresh Meat Fresh meat: Adulthood consumption A3 Case-control studies (4) Four case-control studies examined this exposure in China using study-specific food frequency questionnaires except for the study of Armstrong et al which evaluated exposure with a dietary history questionnaire. The three studies that examined consumption of fresh organ meats at any time prior to diagnosis and consumption of fresh meat and or fresh liver three years prior to diagnosis indicated no significant associations with these foods and NPC but provided no details regarding the conduct of the analysis (Ning et al., 1990, Yu et al., 1989, Yuan et al., 2000b). The study of Armstrong et al showed increased significant associations between NPC and both consumption of fresh liver at age 10 and 5 years prior to diagnosis as well as consumption of other pork/beef organs 5 years prior to diagnosis (Armstrong et al., 1998b). Exposures compared weekly consumption versus less than monthly and trend analysis for the liver consumption was also positive. None of the analyses were adjusted for any confounding variables. Fresh meat: Childhood consumption A3 Case-control studies (4) Four case-control studies examined the risks of NPC associated with childhood consumption of fresh meats. All studies but Armstrong et al used study-specific food frequency questionnaires and all showed no significant associations. The exposures included fresh meat at ages 10 and 1-2 and during weaning and one study specified consumption of fresh liver intake at age 10. None of the studies provided details of the analysis and all adjusted only for age and sex and sometimes area of residence (Ning et al., 1990, Yu et al., 1989, Yu et al., 1988). Only the Armstrong et al study reported a significant positive association with consumption of fresh liver at age 10 or 5 years before diagnosis but not with consumption of other organ meat at age 10 based on a dietary questionnaire (Armstrong et al., 1998b). The comparison of frequency of intake compared to less than monthly yielded a highly significant positive trend but the odds ratio of 2 was not adjusted for any potential confounding variables. 2.5.1.2 Processed meat Processed meat: Adulthood consumption A3 Case-control studies (5) Five case-control studies have examined the relationship of processed meats to the risk of NPC Three studies were done in Chinese in China or in Singapore, one in the Philippines (West et al., 1993) and one in the USA with unknown ethnicity of the subjects (Farrow et al., 1998). All of the studies had between 100 and 250 cases. Four of the studies reported no significant association of consumption of processed meat and the risk of NPC. The Farrow study in the USA found no association with all processed meats based on the NCI food frequency questionnaire and no trend after adjustment for age sex energy intake and alcohol and smoking. The Lee et al study using a study-specific food frequency questionnaire to identify exposure to Chinese sausage found no association or trend after adjustment for age and sex (Lee et al., 1994). The Yu et al study examined liver sausage intake for subjects at age 10 and three years before diagnosis using a food frequency questionnaire and

36

found no association after adjustment for age, sex and salted fish intake but with no details regarding the analysis (Yu et al., 1986). The West et al study of processed meats in general determined from an unspecified assessment instrument found a very low odds ratio of 0.46 based on tertiles of exposure that was of borderline significance when adjusted for the usual variables plus environmental factors, fish intake and herbal medicines. Only the study of Zou et al reported an association (odds ratio 1.8) between smoked processed meats and NPC without any adjustments for potential confounding variables (Zou, 1999).

Forest Plot for Highest vs. Lowest Analysis: Processed Meat, Case-control studies


.05 1 3

Study

Effect size

(95% CI)

NAS00700 (Farrow, 1998) 1.54 ( 0.71, 3.33)

NAS01056 (Lee, 1994) 1.00 ( 0.33, 3.06)

NAS01153 (West, 1993) 0.46 ( 0.21, 1.03)

NAS06023 (Zou, 1999) 1.80 ( 1.09, 2.97)

Processed meat: Childhood consumption A3 Case-control studies (3) Three studies reporting results for processed meat during childhood examined types of sausage and observed no significant associations. The three studies were all done in China and used study-specific food frequency questionnaires to identify exposures. The number of cases in the studies ranged from 128 to 250. All studies adjusted at least for age and sex. All reported that the odds ratios were non-significant for any association but only the Lee et al study reported the actual odds ratio as 0.8 (Lee et al., 1994). Both the Lee et al and the Yu et al study reported the association between Chinese sausage and liver sausage respectively based on exposure at age 10 (Lee et al., 1994, Yu et al., 1988). The Yu et al study reported the association between liver sausage exposure at age 10 years and 3 years before diagnosis as reported under the adult consumption (Yu et al., 1986). 2.5.1.3 Red meat No results found. 2.5.1.3.1 Beef A3 Case-control studies (2) Two case-control studies reported on beef intake in relation to NPC. In a study in Malaysia in which 60 NPC cases were compared to 150 controls, the families of cases were less likely than the families of controls to eat beef with their meals (OR 0.4; p-value <0.05) (Armstrong, 1978, Zheng et al., 1994b).

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A5 Ecological studies (1) An ecologic study in China and Hong Kong also observed an inverse relationship between per capita beef consumption and the occurrence of NPC (Koo et al., 1997). 2.5.1.3.2 Pork Non-processed pork A5 Ecological studies (1) In an ecological study, per capita pork consumption was inversely correlated with NPC rates (Koo et al., 1997). Processed pork A3 Case-control studies (3) Three case-control studies, all implemented in China, reported on the association between processed pork consumption and NPC. The studies ranged in size from 128 cases/174 controls to 250 cases/250 controls, and all used study-specific food frequency questionnaires to measure the dietary exposure. None of the studies reported measures of association, but rather only whether the results were “statistically significant” or not. The one study to report a significant increased NPC risk was for the exposure of “salted pork” (Zheng et al., 1993). Consumption of salted pork or pork sausage at age 10 years or as an adult was reported to be not significantly associated with NPC risk in two other studies (Yu et al., 1986, Yu et al., 1988). 2.5.1.3.4 Organ Meats Non-processed organ meats: Adulthood consumption A3 Case-control studies (4) Of the four case-control studies to report on the association between adult consumption of organ meats and NPC, most have simply reported the findings as being not statistically significant without reporting detailed results (Ning et al., 1990, Yu et al., 1989, Yuan et al., 2000b). The lone exception was the study of Armstrong et al, in which NPC cases were significantly more likely than controls to have more frequently consumed pork/beef liver and other organs during adulthood (Armstrong et al., 1998b). Non-processed organ meats: Childhood consumption A3 Case-control studies (4) Four case-control studies reported on the association between childhood consumption of organ meats and NPC. Liver was specifically measured in all of these studies, and one study additionally measured “other fresh pork/beef organ.” For most of the studies, the results were simply reported as being not statistically significant without reporting detailed results (Ning et al., 1990, Yu et al., 1989, Yu et al., 1988)). The lone exception was the study of Armstrong et al, in which NPC cases were more likely than controls (highest-versus-lowest OR 1.98; 95% CI 0.97-4.05) to have more frequently consumed pork/beef liver and other organs at ten years of age (Armstrong et al., 1998b). Processed organ meats A3 Case-control studies (2)

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Two case-control studies reported on the consumption of processed organ meats during childhood in relation to NPC risk. Both of these studies were carried out by Yu and colleagues in China, and the exposure measured was liver sausage at ten years of age. The results for both studies were reported as being not statistically significant, but without further detail (Yu et al., 1986, Yu et al., 1988). 2.5.1.4 Poultry A3 Case-control studies (2) Two studies, both carried out in northern Africa, reported on the consumption chicken during childhood and NPC risk. After adjusting for age, sex, and area of residence, chicken intake as a baby food was inversely associated with NPC (OR 0.2; 95% CI 0.06-0.60) in a study in Algeria (Laouamri et al., 2001). In contrast to the findings in Algeria, findings from Tunisia indicated that chicken consumption during childhood was strongly associated with increased risk of NPC (OR 4.7) (Jeannel et al., 1990a). A5 Ecological studies (1) An ecologic study in China and Hong Kong observed per capita poultry consumption was inversely related to rates of NPC occurrence (Koo et al., 1997). 2.5.2 Fish (excluding salted fish) Non-preserved fish A3 Case-control studies (3) Three studies from China evaluated intake of fresh fish at varying ages in relation to NPC risk. None of the studies observed significant associations for any of the age groups analyzed. In the first study (Yu et al., 1989), no significant associations were observed among matched cases and controls for intake of fresh fish sauce during adulthood, at age 10, or at ages 1-2. A second study by Yu et al reported similar non-significant associations for fresh fish consumption at age 10, at ages 1-2 (p=0.23), and during weaning (p=0.09) (Yu et al., 1988). Likewise, the third study by Ning et al reported non-significant results for boiled fish consumption during adulthood and at age 10 (Ning et al., 1990). A5 Ecological studies (1) An ecological study of Chinese men and women in Hong Kong examined the association between per capita fish consumption and age-adjusted rates of NPC (Koo et al., 1997). Significant associations were observed for saltwater fish (r2= -0.83, p=0.039 for men and r2= -0.84, p=0.038 for women), but not for freshwater fish (r2= -0.70, p=0.124 for men and r2= -0.77, p=0.070 for women). 2.5.2.1 Salted Fish A2 Cohort studies (1) One cohort study reported on the association between salted fish intake and NPC (Zou, 1994). This study was carried out in Sihui County, Guangdong Province, China. The cohort for the analyses of adulthood consumption of salted fish was based on 505 individuals between the ages of 35-64 years who were followed-up for nine years. During follow-up, 17 cohort members were diagnosed with NPC. The investigators queried about salted fish intake during the decades of the 1960s, 1970s, and 1980s. The results were all unadjusted; no measures of association were presented, with only p-values reported in the text. The p-values comparing salted fish intake at least once per week compared to less frequent consumption were <0.001, 0.014, and 0.21 for consumption in the 1960s, 1970s, and 1980s, respectively. It is difficult to make strong inferences based on small number of NPC cases and the limited information presented, but the results of this cohort study document

39

the temporal association between salted fish intake and NPC risk and suggest that accounting for a longer latency period may strengthen the association between salted fish intake and NPC risk. Salted fish: Adulthood consumption A3 Case-control studies (21) A total of 21 case-control studies reported on the association between salted fish intake during adulthood and NPC. Nine of these studies reported data in sufficient detail to perform a dose-response meta-analysis. The results of the dose-response meta-analysis based on the number of times salted fish was consumed per week during adulthood showed evidence of a strong trend of increasing NPC risk as salted fish intake increased (summary random effects RR 1.28; 95% CI 1.13-1.44 per time/week). B2 Size of effect The magnitude of the summary RR (summary random effects RR 1.28; 95% CI 1.13-1.44 per time/week) observed in the dose-response meta-analyses indicates a strong dose-response association between salted fish intake and NPC. B3 Biological Gradient The dose-response analyses are compatible with a strong dose-response trend between salted fish consumption and NPC, with a summary random effect RRs of 1.28 (95% CI 1.13-1.44 per time/week). The results from all nine of the studies that contributed evidence to the meta-analysis were consistently in the direction of increased risk, with dose-response ORs ranging from 1.06 to 2.50 per time/week. There were three studies each with OR point estimates of 1.06 to 1.20, 1.21-1.50, and >1.50.

Dose-Response Graph: Salted fish intake during adulthood, Case-control studies

40

B4 Internal Consistency/heterogeneity by dietary methodology In these studies, salted fish intake was measured using study specific FFQs or dietary history questionnaires, and was most often referred to as salted fish. All of the studies were hospital-based for case ascertainment. B5 Summary Illustrations of effects (e.g., forest plots)

Forest Plot for Dose-Response Analysis: Salted fish intake during adulthood, Case-control studies

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Odds Ratio, times/week .1 1 5

Study

Effect size

(95% CI) % Weight

NAS00577 (Shanghai China, Yuan, 2000) 1.73 ( 0.66, 4.52) 1.5

NAS01056 (Singapore, Lee, 1994) 1.17 ( 0.85, 1.61) 8.4

NAS01141 (Guangzhou China, Zheng, 1994) 2.50 ( 1.63, 3.85) 5.7

NAS01248 (Thailand, Sriamporn, 1992) 1.35 ( 1.06, 1.72) 11.1

NAS01459 (Guangzhou China, Yu, 1989) 1.10 ( 1.00, 1.21) 18.0

NAS01608 (Hong Kong, Yu, 1986) 1.31 ( 1.13, 1.51) 15.7

NAS06003 (S. Fujian China, Ye, 1995) 1.71 ( 1.08, 2.70) 5.2

NAS06010 (Fujian China, Cai, 1996) 1.06 ( 1.00, 1.12) 19.3

NAS06023 (Yangjiang China, Zou, 1999) 1.32 ( 1.13, 1.54) 15.2

Overall 1.28 ( 1.13, 1.44) 100.0

Forest Plot for Highest vs. Lowest Analysis: Salted fish intake during adulthood, Case-control studies


.01 1 100

Study Effect size (95% CI)

NAS00531 (Taipei Taiwan, Ward, 2000) 0.80 ( 0.52, 1.24)

NAS00577 (Shanghai China, Yuan, 2000) 1.82 ( 0.86, 3.86)

NAS00749 (Selangor Malaysia, Armstrong, 1998) 4.22 ( 2.23, 7.99)

NAS01056 (Singapore, Lee, 1994) 4.40 ( 0.72, 26.76)

NAS01113 (Wuzhou China, Zheng, 1994) 4.07 ( 0.36, 45.80)

NAS01141 (Guangzhou China, Zheng, 1994) 17.20 ( 2.82, 104.79)

NAS01153 (Rizal Phillipines, West, 1993) 1.30 ( 0.67, 2.52)

NAS01248 (Northeast Thailand, Sriamporn, 1992) 2.50 ( 1.20, 5.20)

NAS01459 (Guangzhou China, Yu, 1989) 1.80 ( 0.90, 3.60)

NAS01608 (Hong Kong, Yu, 1986) 7.50 ( 0.88, 63.89)

NAS01922 (Tianjin City China, Ning, 1990) 2.20 ( 1.30, 3.71)

NAS06003 (South Fujian China, Ye, 1995) 5.00 ( 1.27, 19.72)

NAS06009 (Minan Fujian China, Ye, 1995) 2.00 ( 0.88, 4.56)

NAS06010 (Fujian China, Cai, 1996) 1.32 ( 0.98, 1.77)

NAS06021 (Guangxi China, Chen, 1994) 5.51 ( 1.74, 17.44)

NAS06022 (Heilongjiang China, Wang, 1993) 8.99 ( 1.60, 50.44)

NAS06023 (Yangjiang China, Zou, 1999) 3.07 ( 1.66, 5.69)

B6 Gene-nutrient interactions Does not apply.

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C Assessment of heterogeneity within and between study types Within the case-control dose-response meta-analysis, statistically significant heterogeneity was detected, with an I2 statistics of 75%. Inspection of the data reveals that the heterogeneity present relates to the magnitude of the dose-response gradient, not heterogeneity with respect to the presence of a dose-response trend. The results for all nine studies supported the presence of a positive dose-response trend. The source of the heterogeneity may relate to the fact that the two studies with the largest weights also observed the weakest dose-response trends, whereas studies with the smallest weights in the meta-analysis tended to observe strong dose-response trends. D. Factors influencing heterogeneity and meta-regression A factor that could contribute to the variability in the observed magnitude of associations is between-region differences in specific methods of salted fish preparation, and possibly with the type of fish consumed. This could potentially lead to differences in the risk associated with salted fish consumption but this is difficult to rigorously assess with so few studies, leaving an insufficient number of studies per region to analyze separately. E. Important quality issues for interpretation of the evidence The dose-response meta-analyses for case-control evidence for the association between salted fish intake and NPC yielded results compatible with a strong increased risk associated with salted fish intake. An important consideration is the potential confounding factors that have been accounted for in these studies. All nine of these studies included adjustments for at least age and sex, and the majority also controlled for neighborhood of residence. Other factors considered included cigarette smoking (3 studies), alcohol drinking (2 studies), and exposure to other environmental exposures (2 studies). Importantly, other dietary factors were rarely taken into consideration (1 study adjusted for consumption of fermented soy). The absence of information on EBV infection status is particularly notable. The limited extent to which potential confounding variables have been controlled for is thus an important issue affecting the quality of the overall evidence. Seventeen of the case-control studies could be included in highest-versus-lowest categories comparison. The results of this data summary strongly reinforce the evidence suggesting salted fish intake increases the risk of NPC. Of the 17 studies, only one reported an odds ratio of less than unity, whereas four studies reported odds ratios between 1.33 and 1.99, four studies reported odds ratios between 2.0 and 4.0, and in 8 studies odds ratios of greater than 4.0 were observed. Four of the 21 case-control studies that reported information concerning the association between adulthood consumption of salted fish and NPC did not present sufficient data to be included in any of the quantitative data summaries. In a case-control study of 205 NPC cases and 205 controls carried out in China, Zheng et al reported in the text that cases were “significantly” more likely to have the highest salted fish consumption, without reporting a p-value or measure of association (Zheng et al.). In a study in Malaysia comprised of 100 NPC cases and 100 controls, the case-control difference in current salted fish consumption in adults was reported to be not statistically significantly different (Armstrong et al., 1983a). No measure of association or p-value was reported, but the comparison was adjusted for age, sex, area of residence, and ethnicity. Similar results to this were reported in a case-control study conducted in the U.S. (n=156 cases, n=267 controls) (Henderson, 1976). In a much larger study carried out in Taiwan, a comparison of the consumption of moldy and firm salted fish was reported to be not statistically significantly different between 502 NPC cases and 1942 controls (Yang, 2005). Because only minimal information about the results were presented, it is difficult to compare these four studies to those that presented more thorough descriptions of the results. With this caveat, the results of these four studies appear to be less supportive of an association than studies included in the quantitative synthesis of the evidence.

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In summary, the case-control evidence is clear and consistent in suggesting that salted fish intake is associated with increased NPC risk. The evidence to specifically pinpoint the observed risks to salted fish would be more convincing if potential confounding factors had been more completely accounted for.

Funnel Plot for Dose-Response Analysis: Salted fish intake during adulthood, Case-control studies

Begg's funnel plot with pseudo 95% confidence limits

logR

s.e. of: logR0 .2 .4 .6

-1

-.5

0

.5

1

Funnel Plot for Highest vs. Lowest Analysis: Salted fish intake during adulthood, Case-control studies


logR

s.e. of: logR0 .5 1 1.5

-2

0

2

4

F. Mechanisms and animal experimental data More studies have examined the role of nitrosamines and nitrites in salted fish as essential agents for transformation of NPC precursor tissues. Evidence suggests that high intake of nitrate and nitrosamine from salted fish account for some of this increased risk of NPC development. Nitrosamines are known mutagens and animal carcinogens that induce gene mutation through the formation of DNA adducts which if not repaired may lead to point mutations. The N-nitrosamines are a large group of compounds with a common carcinogenic mechanism (Goldman et al., 2003). Salted fish has been shown to contain N-dimethylnitrosamine, N-diethylnitrosamine, N-nitrosopyrrolidene and N-nitrosopiperidine (Zou et al., 1992, Zou et al., 1994). Levels of these compounds were highest in salted fish from areas with the highest NPC mortality, while lower in areas

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with lower NPC mortality (Zou et al., 1992, Zou et al., 1994). Exposure of the nasopharynx to these agents may be particularly damaging in that the carcinogenic properties of nitrosamines are greatest following oral administration. In addition, the variation in nitrosamine content of salted fish may contribute to heterogeneity in assigning risk to salted fish consumption in different geographic locations.

Alkylating agents including nitrosamines produce DNA adducts, specifically 7-methylguanine and O6-methylguanine. The O6-methylguanine is mostly responsible for the mutagenicity and carcinogenicity of these alkylating agents (Goldman et al., 2003). Unfortunately, the genes targeted for mutational alteration in NPC have to a large degree not been identified, which does not allow a definitive association of nitrosamine exposure to tumor suppressor or oncogene mutation. Among the commonly mutated genes in other types of tumors, no reports describe mutation of k-ras and studies of mutation of the retinoblastoma gene(Lin et al., 1992, Sun et al., 1993) and p16/ CDKN2a (Lo et al., 1995, Sun et al., 1995)have all been negative. The most extensively studied gene in NPC for mutational alterations is p53, also the most commonly mutated gene in other malignancies. Ten published studies in the last 12 years have reported mutation of p53 ranging from 0-27% of NPC tumors studied (Burgos, 2003, Chakrani et al., 1995, Effert et al., 1992, Lo et al., 1992, Lung et al., 1998, Nasrin et al., 1994, Spruck et al., 1992, Sun et al., 1992, Van Tornout et al., 1997, Xie et al., 1997), with the 27% result in a study of only 11 tumors(Lung et al., 1998). Overall, 18 of 282 tumors have been found to contain p53 mutations (overall percentage 6%), suggesting that mutations in p53 are not common and do not provide a connection between nitrosamines and the progression of NPC. However, in at least one study (Van Tornout et al., 1997), all 4 of the mutations detected were GC>AT, of particular mechanistic importance for alkylating agents.

The O6-methylguanine leads to GC->AT transitions in cell-culture and animal models if not repaired by O6-methylguanine methyltransferase (MGMT), and as described above, this lesion is produced by alkylating agents. MGMT has been shown to be altered in NPC, although through epigenetic changes, rather than mutational inactivation. Hypermethyaltion of the promoter region of MGMT silences expression of this gene in many cancers (Esteller et al., 1999) which has been reported in 20-28% of nasopharyngeal cancer (Kwong et al., 2002, Wong et al., 2003). Inactivation of MGMT has been shown to be associated with the type of p53 mutations described above in lung and colon cancer(Esteller et al., 2001, Wolf et al., 2001), but due to the infrequent mutations in NPC has not been studied . As noted above, LMP-1 produced by EBV reactivation may also reduce DNA repair capacity, compounding the mutagenic effects of nitrosamine compounds.

Additional support for the importance of nitrosamines in the carcinogenic process of NPC is provided by studies examining the cytochrome p450 enzyme CYP2E1. N-nitrosodimethylamine undergoes enzymatic hydroxylation catalyzed mainly by CYP2E1, a step in the activation of carcinogenic adducts (Goldman et al., 2003). CYP2E1 is expressed in the nasopharynx and in NPC tumors(He et al., 2002). Increased activity of this enzyme would then result in increased activation of pro-carcinogens. A genetic polymorphism in the 5'-flanking region of the human CYP2E1, the C2 allele, affects binding of trans-acting factor to the promoter(Hayashi et al., 1991), This sequence change affects transcriptional regulation, resulting in up to 10-fold differences in promoter activity of the CYP2E1 gene(Hayashi et al., 1991). Studies have demonstrated an increased risk of developing NPC in patients with this variant form(Hildesheim et al., 1997a, Hildesheim et al., 1995, Kongruttanachok et al., 2001), (relative risks of 2-2.5, higher in non-smokers), consistent with the increased formation of carcinogenic nitrosamines from salted fish for those individuals. These studies suggest genetic modifiers of environmental exposure contribute to the risks inherent in consumption of salted fish. Such genetic variation may contribute to the heterogeneity in studies examining risk of NPC following salted fish consumption. Salted fish: Childhood consumption (Age 10) A3 Case-control studies (16)

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A total of 16 case-control studies reported on the association between salted fish intake at approximately 10 years of age and NPC. Nine of these studies reported data in sufficient detail to be included in a dose-response meta-analysis. The results of the dose-response meta-analysis based on the number of times salted fish was consumed per week when 10 years-old showed evidence of a strong trend of increasing NPC risk as salted fish intake increased (summary random effects RR 1.35; 95% CI 1.14-1.60 per time/week). B2 Size of effect The magnitude of the summary RR (summary random effects RR 1.35; 95% CI 1.14-1.60 per time/week) observed in the dose-response meta-analyses indicates a strong dose-response association between salted fish intake at age 10 years and NPC. B3 Biological Gradient The dose-response analyses are compatible with a strong dose-response trend between salted fish consumption and NPC, with a summary random effect RR of 1.35 (95% CI 1.14-1.60 per time/week). The results from eight of the nine studies that contributed evidence to the meta-analysis were in the direction of increased risk, with dose-response ORs ranging from 0.97 to 1.75 per time/week. There were three studies with OR point estimates of 1.10 to 1.20, one study with an OR between 1.21-1.50, and four studies with ORs between 1.51 and 1.75.

Dose-Response Graph: Salted fish intake at age 10, Case-control studies

46

B4 Internal Consistency/heterogeneity by dietary methodology In these studies, salted fish intake was measured using study specific FFQs or dietary history questionnaires. All of the studies were hospital-based for case ascertainment. B5 Summary Illustrations of effects (e.g., forest plots)

Forest Plot for Dose-Response Analysis: Salted fish intake at age 10, Case-control studies

47


Study

Effect size

(95% CI) % Weight


NAS01113 (Wuzhou China, Zheng, 1994) 1.19 ( 0.86, 1.64) 9.9



NAS01520 (Yulin Guangxi China, Yu, 1988) 1.43 ( 0.71, 2.89) 4.2

NAS01608 (Hong Kong, Yu, 1986) 1.74 ( 1.40, 2.16) 12.2

NAS01712 (Selangor Malaysia, Armstrong, 1983) 1.51 ( 1.17, 1.96) 11.3

NAS01922 (Tianjin City China, Ning, 1990) 1.55 ( 1.18, 2.04) 11.0

NAS05679 (Taiwan, Yang, 2005) 1.18 ( 0.91, 1.53) 11.3

Overall 1.35 ( 1.14, 1.60) 100.0

Forest Plot for Highest vs. Lowest Analysis: Salted fish intake at age 10, Case-control studies


.01 1 100

Study

Effect size

(95% CI)



NAS00821 (Taiwan, Hildesheim, 1997) 1.40 ( 0.45, 4.33)





NAS01520 (Yulin Guangxi China, Yu, 1988) 1.50 ( 0.51, 4.40)

NAS01608 (Hong Kong, Yu, 1986) 37.70 ( 14.12, 100.65)


NAS01766 (Alaska US, Lanier, 1980) 4.00 ( 0.57, 28.06)


NAS05679 (Taiwan, Yang, 2005) 1.78 ( 0.82, 3.88)

NAS06020 (Heilongjiang China, Na, 1988) 5.50 ( 0.99, 30.62)

B6 Gene-nutrient interactions Does not apply. C Assessment of heterogeneity within and between study types

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Within the case-control dose-response meta-analysis, statistically significant heterogeneity was detected, with an I2 statistics of 83%. The presence of a dose-response trend was observed so consistently that the heterogeneity present relates primarily to the magnitude of the dose-response gradient, not with respect to the presence or absence of a dose-response trend. The results for eight of nine studies supported the presence of a positive dose-response trend. The relative weights that the studied contributed to the meta-analyses were mostly evenly distributed across many studies. A key source of the heterogeneity may be due to the study in Singapore of Lee et al (Lee et al., 1994), the one study in which a dose-response trend was completely absent. The fact that this was one of the few studies not conducted in China may also be relevant. D. Factors influencing heterogeneity and meta-regression A factor that could contribute to the variability in the observed magnitude of associations is between-region differences in specific methods of salted fish preparation, and possibly with the type of fish consumed. This could potentially lead to differences in the risk associated with salted fish consumption but this is difficult to rigorously assess with so few studies, leaving an insufficient number of studies per region to analyze separately. The one study in which a positive dose-response relationship was absent was a study conducted in Singapore (Lee et al., 1994), one of only two studies included in the dose-response meta-analysis that took place outside of China. E. Important quality issues for interpretation of the evidence The dose-response meta-analyses of case-control studies to assess the association between salted fish intake at age 10 years and NPC yielded results indicating that NPC risk increases markedly with greater intake of salted fish. Clearly, the potential role that confounding factors may be contributing to this statistical association is a key consideration in interpreting this body of evidence. All nine of these studies included adjustments for at least age and sex, and five also further controlled for neighborhood of residence. Other factors considered included indicators of socioeconomic status (2 studies). Importantly, cigarette smoking, alcohol drinking, and dietary factors were not taken into consideration in any of these studies. The absence of information on EBV infection status is particularly notable. The limited extent to which potential confounding variables have been controlled for is thus an important issue affecting the quality of the overall evidence. Another important issue related to quality of the evidence is the remote recall of diet, usually by the mother of the study participant. While the accuracy of reporting may be questionable, the main issue is the degree to which accuracy of reporting may differ by case-control status to introduce a bias. The consistency of the findings across studies conducted by different investigators in different locations suggests either this is unlikely to explain the findings or that the information bias is ubiquitous across studies. The former explanation seems more likely. Fourteen of the case-control studies could be included in highest-versus-lowest categories comparison. The results of this data summary strongly reinforce the evidence suggesting that salted fish intake at 10 years of age increases the risk of NPC. Of the 14 studies, only one reported an odds ratio of less than unity, whereas five studies reported odds ratios between 1.40 and 1.99, three studies reported odds ratios between 2.0 and 4.0, and in 5 studies odds ratios of greater than 4.0 were observed. Two of the 16 case-control studies that reported information concerning the association between childhood consumption of salted fish and NPC did not present sufficient data to be included in any of the quantitative data summaries. In a case-control study of 205 NPC cases and 205 controls carried out in China, Zheng et al reported in the text that cases were “significantly” more likely to have the highest salted fish consumption at age 10 years, without reporting a p-value or measure of association (Zheng et al., 1993). In a study in Malaysia comprised of 100 NPC cases and 100 controls, the case-control difference in current salted fish consumption in

49

children was reported to be statistically significantly different (Armstrong et al., 1983a). This comparison was adjusted for age, sex, area of residence, and ethnicity. In summary, the case-control evidence is clear and consistent in suggesting that salted fish intake in 10-year-old children is associated with increased NPC risk. The evidence to specifically pinpoint the observed risks to salted fish would be more convincing if potential confounding factors had been more completely accounted for.

Funnel Plot for Dose-Response Analysis: Salted fish intake at age 10, Case-control studies


logR

s.e. of: logR0 .2 .4

-.5

0

.5

1

Funnel Plot for Highest vs. Lowest Analysis: Salted fish intake at age 10, Case-control studies


logR

s.e. of: logR0 .5 1

-2

0

2

4

Salted fish: Childhood consumption (Ages 0-3) A3 Case-control studies (10) A total of 10 case-control studies reported on the association between salted fish intake at during 0-3 years of age and NPC. Five of these studies reported data in sufficient detail to be included in a dose-response meta-

50

analysis. The results of the dose-response meta-analysis based on the number of times salted fish was consumed per week when 0-3 years old showed evidence of a strong trend of increasing NPC risk as salted fish intake increased (summary random effects RR 1.42; 95% CI 1.11-1.81 per time/week). B2 Size of effect The magnitude of the summary RR (summary random effects RR 1.42; 95% CI 1.11-1.81 per time/week) observed in the dose-response meta-analyses indicates a strong dose-response association between salted fish intake at ages 0-3 years and NPC. B3 Biological Gradient The dose-response analyses are compatible with a strong dose-response trend between salted fish consumption and NPC, with a summary random effect RR of 1.42(95% CI 1.11-1.81 per time/week). The results from all five of the studies that contributed evidence to the meta-analysis were in the direction of increased risk, with dose-response ORs ranging from 1.21 to 1.84 per time/week. Four studies had OR point estimates of 1.21 to 1.21, with one study of relatively high influence reporting an OR of 1.84.

Dose-Response Graph: Salted fish intake at ages 0-3, Case-control studies

B4 Internal Consistency/heterogeneity by dietary methodology

51

In these studies, salted fish intake was measured using study specific FFQs or dietary history questionnaires. All of the studies were hospital-based for case ascertainment. B5 Summary Illustrations of effects (e.g., forest plots)

Forest Plot for Dose-Response Analysis: Salted fish intake at ages 0-3, Case-control studies

Odds Ratio, times/week

.05 1 4

Study

Effect size

(95% CI) % Weight






Overall 1.42 ( 1.11, 1.81) 100.0

Forest Plot for Highest vs. Lowest Analysis: Salted fish intake at ages 0-3, Case-control studies


.01 1 60

Study

Effect size

(95% CI)







NAS01608 (Hong Kong, Yu, 1986) 20.20 ( 6.79, 60.06)

NAS01812 (Hong Kong, Geser, 1978) 2.60 ( 1.26, 5.37)

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B6 Gene-nutrient interactions Does not apply. C Assessment of heterogeneity within and between study types Within the case-control dose-response meta-analysis, statistically significant heterogeneity was detected, with an I2 statistics of 66%. The presence of a dose-response trend was observed so consistently in all five studies that the heterogeneity present relates primarily to the magnitude of the dose-response gradient, not with respect to the presence or absence of a dose-response trend. D. Factors influencing heterogeneity and meta-regression The only study that exhibited any variation from the narrow range of dose-response associations observed was the steeper dose-response gradient observed in a study conducted in Guangzhou, China (Zheng et al., 1994a). However, another study from this same region also reported findings that were more in keeping with the findings of others (Yu et al., 1989), suggesting that the heterogeneity is not due to regional variation in preservation techniques. E. Important quality issues for interpretation of the evidence The dose-response meta-analyses of case-control studies to assess the association between salted fish intake at ages 0-3 years and NPC yielded results indicating that NPC risk increases markedly with greater intake of salted fish. Clearly, the potential role that confounding factors may be contributing to this statistical association is a key consideration in interpreting this body of evidence. All five of these studies included adjustments for at least age and sex, and three also further controlled for neighborhood of residence. Other factors considered included indicators of socioeconomic status (2 studies). Importantly, cigarette smoking, alcohol drinking, and dietary factors were not taken into consideration in any of these studies. The absence of information on EBV infection status is particularly notable. The limited extent to which potential confounding variables have been controlled for is thus an important issue affecting the quality of the overall evidence. Another important issue related to quality of the evidence is the remote recall of diet, usually by the mother of the study participant. While the accuracy of reporting may be questionable, the main issue is the degree to which accuracy of reporting may differ by case-control status to introduce a bias. The consistency of the findings across studies conducted by different investigators in different locations suggests either this is unlikely to explain the findings or that the information bias is ubiquitous across studies. The former explanation seems more likely. Eight of the case-control studies could be included in highest-versus-lowest categories comparison. The results of this data summary strongly reinforce the evidence suggesting that salted fish intake at 0-3 years of age increases the risk of NPC. Of the eight studies, only one reported an odds ratio of unity, one study reported an odds ratio of 1.20, another 1.30, with the remaining five studies reporting odds ratios of 2.0 or greater. Two of the ten case-control studies that reported information concerning the association between early childhood consumption (0-3 years of age) of salted fish and NPC did not present sufficient data to be included in any of the quantitative data summaries. In a case-control study of 205 NPC cases and 205 controls carried out in China, Zheng et al reported in the text that cases were “significantly” more likely to have the highest salted fish consumption at ages 0-3 years, without reporting a p-value or measure of association (Zheng et al., 1993). Jeannel and colleagues specifically examined consumption of salted anchovies during weaning in a case-control study of 80 NPC cases and 160 controls in Tunisia (Jeannel et al., 1990a). The reported odds ratio was 1.5 with a p-value of 0.5. The results were adjusted for age, sex, area of residence, and living condition score. Thus, the studies not included in the quantitative syntheses of the evidence also tend support the findings observed in the meta-analyses.

53

In summary, the case-control evidence is clear and consistent in suggesting that salted fish intake in children ages 0 to 3 years is associated with increased NPC risk. The evidence to specifically pinpoint the observed risks to salted fish would be more convincing if potential confounding factors had been more completely accounted for.

Funnel Plot for Dose-Response Analysis: Salted fish intake at ages 0-3, Case-control studies


logR

s.e. of: logR0 .2 .4 .6

-1

0

1

2

Funnel Plot for Highest vs. Lowest Analysis: Salted fish intake at ages 0-3, Case-control studies


logR

s.e. of: logR0 .2 .4 .6

-1

0

1

2

3

Salted fish: Mother’s consumption during pregnancy or breastfeeding A3 Case-control studies (3) Three case-control studies reported on the relationship between NPC and mother’s consumption of salted fish during pregnancy or while breastfeeding. Two of these studies were carried out in China, and the other took place in Singapore among individuals of Chinese ethnicity. Both of the studies conducted in China were carried out by Yu and colleagues. In the first of these studies, comparing 128 NPC cases with 174 controls, Yu and

54

colleagues observed that both consumption of salted fish during pregnancy and during nursing were associated with increased subsequent risk of NPC in the offspring (Yu et al., 1988). The odds ratios for these associations were consistent with a greater than three-fold increased risk with 95% confidence intervals that did not overlap unity after adjusting for age and sex. These results were corroborated in the second of the studies carried out in China, also by Yu and colleagues (Yu et al., 1989), in which the odds ratios for these associations were consistent with a greater than two-fold increased risk with 95% confidence intervals that did not overlap unity after adjusting for age, sex, and neighborhood. These results were based on a comparison of 306 NPC cases with 306 controls. In the study conducted in Singapore by Lee and colleagues, 49 NPC cases were compared to 96 controls, and the results were adjusted for age, sex, ethnicity, and education (Lee et al., 1994). Due to the smaller sample size, among other factors, the 95% confidence intervals were quite wide, but the point estimates of the odds ratios for maternal salted fish consumption during pregnancy (1.3) and during breastfeeding (2.0) were again in the direction of increased risk, although the associations were weaker than in the studies conducted in China.

The results of these three studies thus provide evidence that maternal salted fish consumption during pregnancy and breastfeeding is statistically associated with subsequent risk of NPC in offspring. Prominent among the many factors that have not been accounted for in these studies is whether this observed association is due this measured exposure simply because it is a marker of subsequent salted fish consumption by the index youth. 2.5.2.2 Other preserved fish (excluding salted fish) A2 Cohort studies (1) A cohort study of 505 men and women from China reported unadjusted associations for salted and dried fish consumption during different decades and NPC (Zou, 1994). Any consumption during the 1960’s, 1970’s, or 1980’s was reported as significantly associated when compared to no consumption (p<0.001 for all decades). A3 Case-control studies (5) Five case-control studies contributed evidence concerning intake of non-salted fish and NPC. A meta-analysis was not feasible, however, because several of these studies only reported non-significant associations in the text without details (Ning et al., 1990, Yu et al., 1989, Yu et al., 1988). In a study by Lee et al, risks for various types of preserved fish were examined for different age groupings (Lee et al., 1994). Their only significant finding was for dried, unsalted fish consumed at age 10 (OR=0.1, 95% CI: 0.01-1.0). Other exposures they investigated included dried, tiny fish; dried, tiny fish soup; preserved cuttlefish; preserved fish tidbits; and fish gravy, but none were observed to be significantly associated with NPC at any age group. Intake of fermented fish sauce at different ages was evaluated in a Chinese study by Yu et al (1989). Although no estimates of risk were provided, no significance was reported for highest-versus-lowest analyses or over trends at any age of intake. Likewise, Yu et al (1988) reported no significant association for the consumption of fermented fish paste at age 10. In the same Chinese study by Yu et al (1988), dried fish was observed to be a significant risk factor when consumed at age 10 (OR=6.4, 95% CI: 1.6-26.8), but not at ages 1-2 (OR=2.2, 95% CI: 0.9-5.3). Dried anchovies, consumed during adulthood or at age 10, were not associated with NPC in another Chinese study by Ning et al. The fifth study by Armstrong et al examined the relationship between dried fish consumed during meals and NPC among Chinese in Malaysia (Armstrong, 1978). A significant association was reported when dried fish was consumed at breakfast, but no direction or estimate of risk was offered. When consumed in 3 daily meals, no association between dried fish and NPC was observed. 2.5.3 Shellfish and other seafood Non-preserved seafood

55

A3 Case-control studies (4) Four case-control studies examined the association between shellfish and the risk of NPC. All studies included only persons of Chinese background. Two studies were done in China and used study-specific food frequency questionnaires. These studies included 100 cases (Ning et al., 1990) and 935 cases (Yuan et al., 2000b). Both of these studies reported no significant association of the cancer with exposures to fresh seafood generally (Yuan et al., 2000b) and crab or fresh jellyfish consumed at age 10 and in the three years prior to diagnoses in separate analyses. No details were given regarding the analyses. Both studies of Armstrong et al were done in Malaysia and used a dietary history questionnaire or recall. The early study found a protective effect associated with the family eating prawns at the evening meal or any meal with a significant odds ratio of 0.7 with adjustment for age, sex, race, SES, residence and lifestyle factors (Armstrong, 1978). The later study examined the risks associated with consumption of shrimp at age 10 as well as five years prior to diagnosis and a lifetime exposure (Armstrong et al., 1998b). Only the unadjusted odds ratio for consumption of shrimp at age 10 showed a significantly low association although the lifetime exposure adjusted for SES as well as other food intakes had a borderline significant negative association with an odds ratio of 0.83 (p=.082). Preserved seafood: Adulthood consumption A3 Case-control studies (5) Five case-control studies examined the association between NPC and consumption of different forms of preserved seafood; however only 3 provided sufficient information to be included in a meta-analysis. All studies evaluated exposures through the use of study-specific food frequency questionnaires. All studies included Chinese cases and controls. None of the studies showed significant odds ratios or trends with the different foods although all that reported odds ratios were in the positive direction. Yuan et al examined the association of intake of salted food pastes using 935 controls and found a non-significant association (odds ratio 1.44 p=0.07) after adjustment for age, sex, education and other lifestyle and environmental factors (Yuan et al., 2000b). Lee et al studied the association between dried oysters and dried prawns and found no significant association after adjustment for basic variables (Lee et al., 1994). Yu et al studied the association of consumption of salted fish paste at 3 years prior to diagnosis and at an unknown time and found no association after adjustment for basic variables as well as other suspect foods (Yu et al., 1989). The earlier study of Yu et al examined the risks of eating dried shrimp both in childhood and 3 years prior to diagnosis and found no association after adjustment for possible confounding variables (Yu et al., 1986). Ning et al studied the intake of salted shrimp paste as well as dried shrimp and found no significant associations in the adjusted odds ratios (Ning et al., 1990). Preserved seafood: Childhood consumption A3 Case-control studies (5) Four of the studies investigating adult consumption and one additional study by Yu et al examined the risks of NPC associated with eating of preserved foods in childhood. Only 2 studies provided sufficient data for a meta-analysis. All studies examined exposure through the use of a study-specific food frequency questionnaire. All of the studies adjusted for at least age and sex in some of the analyses. With the exception of salted shrimp paste, all other exposures examined showed no association with NPC and exposure in childhood. Lee et al examined consumption of dried prawns and dried oysters and found no association with exposure at age 10 to either food (Lee et al., 1994). Yu 1988 and 1986 and Ning et al examined the risks associated with consumption fermented crab or shrimp pastes at age 10 as well as dried shrimp at age 10 and combined with adult exposure and found no association even after adjustment for basic variables (Ning et al., 1990, Yu et al., 1986, Yu et al., 1988). However, when Yu 1989 and Ning et al examined the risks of NPC associated with the consumption of salted shrimp paste at age 10 both authors reported a significant association either as a trend (Yu et al., 1989) or

56

as an odds ratio (OR = 3.2 p=0.007) with adjustments for not only the basic variables but for others such as salted fish consumption. Yu 1989 also reported a borderline significant trend (0.07) for this exposure at the ages of 1-2 years in children. 2.5.4. Eggs Non-preserved eggs A3 Case-control studies (4) Four studies examined the risks of NPC associated with consumption of fresh eggs at different ages in Chinese from China (three studies) and Malaysia (Armstrong, 1978). All studies used a study-specific food frequency questionnaire except for Armstrong et al who measured exposures through recall. All studies adjusted for the basic variables of age and sex for at least some of the analyses with the exception of Yuan et al. None of the studies showed an association with exposure to fresh eggs at any age (Yuan et al., 2000b) or three years before diagnosis (Yu et al., 1989), at age 10 years, at 1-2 years (Yu et al., 1989, Yu et al., 1988), or at weaning (Yu et al., 1988) with the exception of the Armstrong et al study that indicated a significant negative association for consumption of eggs by the family at evening meals. However, the same study showed no association with family consumption of eggs at other meals. A5 Ecological studies (1) In a study by Koo et al, per capita consumption of eggs in Hong Kong was analyzed in relation to NPC (Koo et al., 1997). No significant associations were reported for men (r2= -0.42, p=0.405) or women (r2= -0.14, p=0.796). Salted eggs: Adulthood consumption A3 Case-control studies (5) Five case–control studies examined the risk of NPC associated with the consumption of salted eggs with conflicting results; however, only 3 provided the necessary data for a meta-analysis. All studies were conducted in Chinese but the Armstrong studies were done in Malaysia and the others in China. Lee et al and Ning et al used a food frequency questionnaire and examined either the intake of unspecified salted eggs in adulthood or intake of specific chicken or duck eggs three years before diagnosis and found no significant association (Lee et al., 1994, Ning et al., 1990). Armstrong et al examined the risk of family consumption of salted eggs at meals and reported no association (Armstrong, 1978). However, a later study by Armstrong showed a significant association and trend from consumption of salted eggs with exposure derived from a dietary history and adjustment for several other food variables (Armstrong et al., 1998b). The crude odds ratio of 2.55 and the trend were significant and the odds ratio remained significant but lower after adjustment for various foods. The adjusted ratio from the Ward et al study was similar using exposure data from a dietary questionnaire (OR= 2.00) (Ward et al., 2000). Salted eggs: Childhood consumption A3 Case-control studies (4) Four case-control studies examined the risks of NPC associated with the consumption of salted eggs in childhood. All studies were done in Chinese but the study of Armstrong et al and Lee et al were done in Malaysia and Singapore respectively (Armstrong et al., 1998b, Lee et al., 1994). All studies determined the exposure based on a study-specific food frequency questionnaire except for the study of Armstrong et al that used a dietary history questionnaire. The Armstrong study of 282 cases examined the risks at age 10 and found a significant odds ratio without adjustment as well as an association between NPC and lifetime exposures to

57

salted eggs at both age 10 and 5 years prior to diagnosis after adjustment for basic variables and other foods (OR = 1.24). Yu et al studied the risks of exposure to salted eggs at weaning in 128 cases and found a borderline significant association (OR= 5.0 CI 1.2-21) following adjustment with very wide confidence intervals (Yu et al., 1988). The studies of Lee et al and Ning et al with 149 and 100 cases respectively found no association from exposure to salted eggs at age 10 (Lee et al., 1994, Ning et al., 1990). Preserved eggs A3 Case-control studies (5) Five case-control studies examined the risk of NPC associated with the consumption of preserved eggs; however, only 2 provided sufficient data to be included in a meta-analysis. All studies included Chinese from either Singapore (Lee et al., 1994) or China All used study-specific food frequency questionnaires to identify exposures. None of the five studies indicated significant associations between the cancer and preserved eggs of any kind. The studies of Yuan et al and Lee et al adjusted the odds ratios for several demographic variables (Lee et al., 1994, Yuan et al., 2000b). These studies examined the risks from exposure to either unspecified types of preserved eggs or century eggs from exposures at age 10 and in adulthood. The odds ratios and the trends were not significant. The other three studies did not specify the odds ratios but simply reported no significant associations between the cancers and salted dried and tinned eggs and fermented duck eggs at 10 years of age or 3 years prior to diagnosis (Ning et al., 1990, Yu et al., 1988, Zheng et al., 1994b). 2.6 Fats, oils and sugars A3 Case-control studies (3) A total of three case-control studies reported on associations between consumption of fats and oils and risk of NPC. In a case-control study of Chinese in Malaysia, the authors noted in the text that use of cooking oils and fats were not significantly associated with NPC, but the actual quantitative results were not presented (Armstrong, 1978). A study carried out in Algeria reported on the exposures of “dried, salted fat” in addition to a general measure of fat intake. A strong increased risk of NPC (OR 9.2; 95% CI 3.9-21.5) was noted with current consumption of dried, salted fat, after adjusting for age, sex, and neighborhood (Laouamri et al., 2001). In this same study population, the measure of fat intake also exhibited an association in the direction of increased risk that was less robust (OR 2.4; 95% CI 0.9-6.6). One study focused specifically on cod liver oil in early life, measured in infancy and at age 10 years. This study was of people of Chinese ethnicity who resided in Singapore. The results were adjusted for age, sex, ethnicity, and education. The association for consumption at age 10 was null, but during infancy the association was imprecise but in the protective direction (OR 0.5; 95% CI 0.1-2.0) (Lee et al., 1994). 2.6.1 Animal fats A3 Case-control studies (3) Three case-control studies reported on the association between consumption of animal fat and NPC. Two of these studies were carried out in northern Africa, and the other took place in China. The exposure categories considered were heterogeneous, comprised of butter and rancid butter in one study, sheep’s tail fat consumption during childhood in another study, and pork fat in the third study. On these grounds alone, the comparability of results across studies is questionable. In the study in Algeria, as a cooking medium, butter was not clearly associated with increased NPC risk but consumption of rancid butter was strongly associated with increased risk of NPC (OR 7.6; 95% CI 3.5-16.4), after adjusting for age, sex, and area of residence (Laouamri et al., 2001). In the study that took place in Tunisia, comprised of 80 NPC cases and 160 controls, the association between NPC and consumption of sheep’s tail fat during childhood was in the risk direction (OR 3.4; p-value 0.09) after adjusting for age, sex, neighbourhood, and lifestyle factors (Jeannel et al., 1990a). The study in

58

China compared pork fat consumption in 122 NPC cases and 122 controls. After adjusting for age, sex, income, environmental exposures, and numerous dietary factors including salted fish consumption, the investigators reported pork fat consumption was associated with decreased risk of NPC (OR 0.25; p-value 0.025) (Wang, 1993). 2.6.2 Plant oils A3 Case-control studies (4) A total of four case-control studies reported on the relationship between dietary intake of plant oils and the occurrence of NPC. One of these studies took place in Algeria, another in Singapore, and two in China. These studies have yielded mixed results. In the study in Algeria, plant oils such as sunflower oil and olive oil used as a cooking medium were associated with decreased risk of NPC but with wide confidence limits that overlapped unity (Laouamri et al., 2001). In this same study, intake of olive oil in seasonings was more clearly inversely associated with lower risk of NPC (OR 0.35; 95% CI 0.15-0.79) (Laouamri et al., 2001). In the study of Chinese in Singapore, more frequent margarine consumption at age 10 was inversely associated with NPC risk (OR 0.6; 95% CI 0.3-1.1), after adjusting for age, sex, ethnicity, and education (Lee et al., 1994). In one of the studies in China, fennel oil consumption at age 10 was reported as being not statistically significantly associated with NPC risk without details (Yu et al., 1988). In the other study in China, Wang and colleagues observed that plant oils were associated with NPC in the direction of increased risk (OR 4.3; p-value 0.001), after adjusting for factors that included age, sex, and environmental and dietary factors (Wang, 1993). 2.6.3 Hydrogenated fats and oils No results found. 2.6.4 Sugars A3 Case-control studies (1) In Algeria, Laouamri et al investigated the practice of giving a piece of sugar during teething, and observed that this was associated with increased risk of NPC (OR 2.2; 95% CI 1.1, 4.5). The results were adjusted for age, sex, area of residence (Laouamri et al., 2001). 2.7 Milk and dairy products A3 Case-control studies (4) Four case-controls studies have reported findings on consumption of milk and dairy products in relation to NPC, one in Algeria, one in Malaysia, and two in China. The specific dietary factors investigated have included powdered milk, animal milk, fresh milk, cow’s milk, milk, milo (fortified and flavored powdered milk drink), and horlicks (fortified and flavored powdered milk drink). It readily becomes apparent that within the exposure category of “milk” a wide array of specific exposures are represented. Not surprisingly under these circumstances, the results relating milk drinking to NPC have not yielded consistent findings. The results for fresh milk or cow’s milk were not indicative of being strongly associated with NPC risk. Among Chinese in Malaysia (Armstrong, 1978), drinking fresh milk was not associated with NPC risk overall, but was significantly associated with lower risk in specific subgroups, such as Cantonese. Armstrong and

59

colleagues reported that drinking milk with daily meals, measured as a dichotomous yes/no variable, was observed to be protective (OR 0.6; p<0.01) (Armstrong, 1978). The two studies in China (Yu et al., 1989, Yuan et al., 2000b) reported that the findings between NPC and cow’s milk consumption at age 10 and as an adult and drinking fresh milk were not statistically significant in the text, without presenting measures of association. Other forms of milk consumption, such as powdered milk and fortified and flavored powdered milk drinks (milo, horlicks) also did not appear to be strongly associated with NPC risk. In the study in Algeria, powdered milk was not strongly associated with NPC risk (Laouamri et al., 2001) In the Malaysian study, the association between NPC and the fortified and flavored powdered milk drink milo was null and similar findings were observed for horlicks (Armstrong, 1978). 2.8 Herbs, spices, condiments Herbal, spices, and condiments: Childhood consumption A3 Case-control studies (3) Three case-control studies, all from China, evaluated herbs, spices, and condiments consumed during childhood and NPC. In a study by Ward et al, a significant odds ratio of 2.3 (95% CI: 1.1-4.7) was reported for intake of herbs, spices, and condiments at age 10 when maximally adjusted for age, sex, ethnicity/race, subjects with mothers’ questionnaire and total caloric intake (Ward et al., 2000). Zheng et al observed no significant association for herbal mixtures consumed during weaning or childhood (OR=1.8, p=0.07) (Zheng et al., 1994b). Yu et al reported non-significant associations for various condiments, including hot pepper paste, soy sauce, fish sauce, and oyster sauce, consumed at age 10 (Yu et al., 1988). Herbal intake A3 Case-control studies (6) The evidence for herbal intake did not conform to the requirements for the preferred dose-response approach, but a sufficient number of studies to perform meta-analyses were available for the approach of analyzing highest-versus-lowest categories. A total of four case-control studies contributed data to these analyses. The odds ratios were significantly greater than unity in three of the studies, but a protective association was observed in one study (Armstrong, 1978, Geser et al., 1978, Henderson, 1976). All of the studies adjusted for several variables in the analysis including not only the basic demographic variables but salted fish, personal tobacco consumption, other environmental exposures, and even EBV in one study. Consumption of herbs has primarily been studied in relation to herbal medicines. Studies of herbal medicines in Asia have tended to observe strong risk associations. In India, use of herbal nasal drops were strongly associated with NPC risk (Chelleng et al., 2000), but the study included only 47 cases and the confidence intervals were very wide. In the Philippines, users of herbal medicines were observed to be at significantly higher risk of NPC compared to nonusers (Hildesheim et al., 1992, West et al., 1993). Odds ratios well in excess of unity have also been associated with used of herbal medicines in studies in China (Lin, 1973, Lin et al., 1986), but these studies were not included in the meta-analyses because details were lacking. A case-control study in the U.S. observed an association in the protective direction (OR 0.5; p=0.04) (Henderson, 1976). Most studies only used a never versus ever exposure categories.

Forest Plot for Highest vs. Lowest Analysis: Herbal intake, Case-control studies

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.01 1 100

Study

Effect size

(95% CI)

NAS00544 (Chelleng, 2000) 58.40 ( 7.93, 430.32)

NAS01153 (West, 1993) 2.50 ( 1.14, 5.49)

NAS01251 (Hildesheim, 1992) 2.60 ( 1.44, 4.71)

NAS04928 (Henderson, 1976) 0.50 ( 0.26, 0.97)

Non-preserved spice intake A3 Case-control studies (3) Three case-control studies examined the association of .NPC and non-preserved spice intake. All the exposures differed. Two studies measured exposures in Chinese either in China (Geser et al., 1978) or in Malaysia (Armstrong, 1978) and both showed no significant association with consumption of vinegar or use of sauces by families of participants. The third study examined risks in Algerians using a food frequency questionnaire (Laouamri et al., 2001). The study showed a significant association with exposure to black pimento at least once a week (OR =10.6) and exposure to mint (OR = 3.2) both of which values are significant after adjustment for age, sex, and area of residence. Preserved spice intake A3 Case-control studies (4) Four case-control studies examined the risk of NPC and exposure to preserved spices. Laouamri (Laouamri et al., 2001) studied Algerians and the other studies included Chinese from China or in one case from Malaysia (Armstrong, 1978). Two studies used study-specific food frequency questionnaires and the others dietary recall (Armstrong, 1978, Ward et al., 2000). Two studies reported on the risks based on consumption in households of either mustard paste (Geser et al., 1978) or pickle chili and both found significant negative associations. Geser et al also found no association with direct consumption of cases. The study of Ward et al also reported no association of cancer with direct consumption of hot chili sauce (Ward et al., 2000). The only significant positive associations were from the Algerian study which evaluated harissa, dried peppers and pickled peppers, all of which spices showed significant associations with adjusted odds ratios ranging from 2.85 to 5.5 for the different exposures. The number of cases included in this study was 72 and the range of case size for all studies was 60 to 375. Soy sauce A3 Case-control studies (3) Three case-control studies have examined the association of NPC with consumption of soy sauce. The studies used food frequency questionnaires except for the study of Armstrong et al that used recall as an assessment

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tool (Armstrong, 1978, Shanmugaratnam et al., 1978, Yuan et al., 2000b). The Armstrong et al study also evaluated the characteristics of the family exposure rather than the individual. One study had two sets of controls (Shanmugaratnam et al., 1978). All studies were in Chinese and most reported several factors used in adjustment. All studies resulted in non-significant associations between soy sauce and NPC. Other fermented condiment intake A3 Case-control studies (2) Two case-control studies evaluated other fermented condiments in relation to NPC. Both studies included Chinese men and women, one in China (Yuan et al., 2000b)and the other in Hong Kong (Geser et al., 1978). No significant associations were reported for the consumption of fish sauce or oyster sauce in either study. 2.9 Composite Foods Mixed vegetables A3 Case-control studies (3) Mixed vegetables, including starchy and non-starchy vegetables, were evaluated in 3 case-control studies. All reported results in the protective direction, but not all reached significance. Green beans and peas were reported as significantly protective for NPC (OR=0.77, 95% CI: 0.62, 0.99) when maximally adjusted for in a Chinese study of 935 cases and 1032 controls (Yuan et al., 2000b). In a study of Chinese in Malaysia (Armstrong et al., 1998b), which included 282 cases and 282 controls, green beans and peas were significantly associated with NPC when consumed during adulthood (OR=0.60, 95% CI: 0.37-0.98), but not at age 10 (OR=0.88, 95% CI: 0.47-1.62). Armstrong et al also observed a significant protective association for carrots and sweet potatoes consumed during adulthood (OR=0.48, 95% CI: 0.28-0.83), but not at age 10 (OR=0.67, 95% CI: 0.33-1.27). In a US study of 140 cases and 208 controls (Farrow et al., 1998), a highest-versus-lowest odds ratio of 0.59 (0.29-1.22) was reported for yellow vegetables, including winter squash, carrots, and yams after adjusting for age, sex, alcohol consumption, smoking habits, and energy intake. Foods with sauces or pastes A3 Case-control studies (3) Three studies reported results for various foods consumed with sauces or pastes. In a study from Algeria (Laouamri et al., 2001), 72 cases and 72 controls were matched by age, sex, and area of residence. Various combinations of hot sauce and foods were shown to be in the direction of risk for NPC, with 5 of 7 exposures being significantly associated: (1) hot sauce with stews, OR=11.3 (95% CI: 4.2-28.5); (2) hot sauce with fried foods, OR=5.5 (95% CI: 2.2-14.0); (3) hot sauce with pulses, OR=4.5 (95% CI: 2.0-9.9); (4) hot sauce with couscous, OR=2.5 (95% CI: 4.1-37.9); (5) hot sauce with pasta, OR=8.0 (95% CI: 1.4-45.8); (6) hot sauce with bread and butter, OR=6.0 (95% CI: 0.6-60.5); and (7) hot sauce with salad, OR=7.0 (95% CI: 0.8-60.6). In a study of Chinese in Singapore (Lee et al., 1994), Chinese rojak, a salad containing prawn paste, was not observed to be associated with NPC when consumed at age 10 (OR=0.9, 95% CI: 0.3-2.2) or during adulthood (OR=1.6 (95% CI: 0.4-5.9) after adjusting for age, sex, education, and ethnicity/race. Belachan, prawn and chilli paste was reported to be significantly associated with NPC in the same study when consumed during adulthood, but no other details were provided. Consumption at age 10 was in the direction of risk, but was not significant (OR=1.8, 95% CI: 0.6-5.3). A study from Tunisia (Jeannel et al., 1990a), which included 80 cases and 160 controls, observed an adjusted odds ratio of 6.5 for consumption of harissa, olive oil, and bread during weaning, but provided no information about the significance of the finding. Foods with rice or noodles

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A3 Case-control studies (2) Two case-control studies evaluated the association between NPC and foods with rice and noodles. Both studies were done in Chinese, one in China and one in Malaysia. Zheng et al used a food frequency questionnaire to examine the risk associated with consumption of salted fish in rice porridge before age 2 and between ages of 2 and 10 and found significant associations with adjusted odds ratios of 3.8 and 3.2 for the two ages (Zheng et al., 1994b). The exposure categories were rarely, monthly and weekly. Armstrong et al studied the risks for family consumption at various meals of rice or noodles with meat, fish or eggs and found no association (Armstrong, 1978). ‘Cooling drink’ A3 Case-control studies (4) Four case-control studies examined the association between the consumption of various cooling drinks and NPC. Three studies by Yu reported the risks related to consumption of cooling soup, a medicinal drink, at age 10 (Yu et al., 1989, Yu et al., 1988) at 3 years prior to diagnosis (Yu et al., 1989) and at both age 10 and 3 years before diagnosis (Yu et al., 1986) and found no significant association of this exposure with NPC. The fourth study of specifies only a “cooling drink” and found no association using two sets of controls (Shanmugaratnam et al., 1978). All studies reported adjusting for the basic variables. Preserved composite foods A3 Case-control studies (4) Four case-control studies examined different types of composite foods in relation to the risk of NPC. Three studies were done in Chinese and one in the USA with mixed ethnicity. All used food frequency questionnaires except for Henderson et al which used an interview (Henderson, 1976). Results varied, possibly because of different exposures. The only significant positive association was reported by Yuan et al in which the interactive effects of preserved foods versus citrus was compared by high, medium and low exposures to each with the reference being high citrus and low preserved food intake (OR = 3.19) (Yuan et al., 2000b). Geser et al examined household consumption of tinned food with fish and Henderson et al examined salted snacks; both found significantly low associations (Geser et al., 1978, Henderson, 1976). Lee et al found no association with salted beef or malt extract. No studies examined the same exposures in this category (Lee et al., 1994). Other composite foods A3 Case-control studies (2) Two case-control studies examined varied foods in relation to the risk of NPC. Armstrong et al examined the consumption of dumplings and soup by the family at various meals and found case families had significantly lower consumption of soup at evening meals and significantly higher consumption of dumplings at breakfast compared to control families (Armstrong, 1978). However, these odds ratios are unadjusted and when consumption of dumplings is examined for all meals the ratios are not significant. Jeannel et al examined the risks associated with the intake of a stewing mixture of peppers and other spices at weaning and in the year prior to diagnosis (Jeannel et al., 1990a). Both adjusted odds ratios were significant and higher for exposure at weaning (OR = 8.4) than for the recent exposure (OR= 4.4). 3 Beverages 3.1 Total fluid intake

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A3 Case-control studies (1) In a case-control study in Malaysia, Armstrong et al (1978) observed that families of NPC cases had drinks at breakfast significantly less often than the families of controls, but this result was only presented in the text without any form of quantification (Armstrong, 1978). 3.2 Water A3 Case-control studies (2) In a case-control study in Algeria, compared to having spring water as a source of drinking water, the odds ratio for having well water as a source of drinking water was non-significantly elevated (OR 7.0); on the other hand, residential access to a piped water supply was associated with reduced risk of NPC(OR 0.2) (Laouamri et al., 2001). In a case-control study in Malaysia, being in a family that drank water with three meals per day was associated with increased risk of NPC compared to being in a family that did not drink water with three meals per day (adjusted OR 1.4, p-value <0.01) (Armstrong, 1978). 3.3 Milk A3 Case-control studies (4) Four case-control studies have reported findings on consumption of milk and dairy products in relation to NPC, one in Algeria, one in Malaysia, and two in China. The specific dietary factors investigated have included powdered milk, animal milk, fresh milk, cow’s milk, milk, milo (fortified and flavored powdered milk drink), and horlicks (fortified and flavored powdered milk drink). It is apparent that within the category of milk these represent a wide array of specific exposures. Not surprisingly under these circumstances, the results relating milk drinking to NPC have not yielded consistent findings. The results for fresh milk or cow’s milk were not indicative of being strongly associated with NPC risk. Among Chinese in Malaysia (Armstrong, 1978), drinking fresh milk was not associated with NPC risk overall, but was significantly associated with lower risk in specific subgroups, such as Cantonese. Armstrong and colleagues reported that drinking milk with daily meals, measured as a dichotomous yes/no variable, was observed to be protective (OR 0.6; p<0.01) (Armstrong, 1978). The two studies in China (Yu et al., 1989, Yuan et al., 2000b) reported that the findings between NPC and cow’s milk consumption at age 10 and as an adult and drinking fresh milk were not statistically significant in the text, without presenting measures of association. Other forms of milk consumption, such as powdered milk and fortified and flavored powdered milk drinks (milo, horlicks) also did not appear to be strongly associated with NPC risk. In the study in Algeria, powdered milk was not strongly associated with NPC risk (Laouamri et al., 2001) In the Malaysian study, the association between NPC and the fortified and flavored powdered milk drink milo was null and similar findings were observed for horlicks (Armstrong, 1978). 3.4 Soft drinks No results found. 3.4.1 Sugary No results found. 3.4.2 Carbonated

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No results found. 3.5 Fruit juices A3 Case-control studies (1) The sole study to examine fruit juice drinking in relation to NPC was a case-control study of 282 cases and 282 matched controls in Malaysia. Compared to those who drank fruit juice less than monthly 5 years prior to the index date of the case’s diagnosis, the odds ratio for those who drank orange juice less than weekly was 0.50 (95% CL 0.31, 0.82) and for those who drank more than weekly was 0.85 (95% CL 0.51, 1.42). For orange juice consumption at age 10 years the corresponding odds ratios were 0.14 (95% CL 0.03, 0.64) and 0.60 (95% CL 0.17, 2.15) for less than weekly and more than weekly consumption, respectively (Armstrong et al., 1998b). 3.6 Hot drinks A3 Case-control studies (1) In results that were presented without detail, it was noted that families of NPC cases were no more likely than the families of controls to drink coffee or tea for breakfast (Armstrong, 1978). 3.6.1 Coffee A3 Case-control studies (3) Of the three studies to assess the relationship between coffee drinking and NPC, two were conducted in the United States, and one study was conducted in Malaysia. All three of the studies used a simple dichotomization of coffee drinking, using either one cup per day versus less or any-versus-no coffee drinking. In the studies conducted in the United States, no associations were observed among drinkers of either regular or decaffeinated coffee (Henderson, 1976, Mabuchi et al., 1985). Among Chinese in Malaysia, those who drank coffee with three meals per day had significantly lower risk of NPC (OR 0.8; p<0.05) than those who did not (Armstrong, 1978). 3.6.2 Tea Tea: Adulthood consumption A3 Case-control studies (7) The evidence for drinking tea did not conform to the requirements for the preferred dose-response approach, but sufficient evidence was available to carry out a meta-analysis using the approach of highest-versus-lowest categories. A total of four case-control studies contributed data to these analyses. Two studies (Henderson, 1976, Mabuchi et al., 1985) included varied ethnic groups and were conducted in the USA. All other studies included Chinese and were located in China, Singapore, Taiwan and Malaysia. Two studies reported a negative association with any tea consumption (Henderson, 1976) or with consumption at three meals a day (Armstrong, 1978). All other studies but one (Zheng et al., 1994b) reported no significant association between tea drinking and risk of NPC. The Zheng et al study reported a significant association between consumption of herbal tea in the year before diagnosis (OR = 4.2) with the odds ratio being adjusted for the basic variables and environmental and food intakes. The latter study is the only one that specifically designated herbal tea consumption.

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One study conducted in the U.S. reported non-significant findings (Mabuchi et al., 1985), in comparison to the observation that any use of tea was associated with decreased NPC risk in the other U.S. study (Henderson, 1976). Shanmugaratnam et al reported non-significant odds ratios of 1.17 using ENT controls and 1.38 using non-ENT controls for Chinese tea (Shanmugaratnam et al., 1978). A case-control study conducted in China was not included in the meta-analysis because of lack of detailed results, but the text indicated an association that was not statistically significant (Lin, 1973).

Forest Plot for Highest vs. Lowest Analysis: Tea, Case-control studies


.01 1 10

Study

Effect size

(95% CI)

NAS01113 (Zheng, 1994) 4.20 ( 1.33, 13.27)

NAS04928 (Henderson, 1976) 0.50 ( 0.27, 0.91)

NAS04944 (Armstrong, 1978) 0.50 ( 0.29, 0.85)

NAS06023 (Zou, 1999) 1.10 ( 0.57, 2.10)

Tea: Childhood consumption A3 Case-control studies (1) One study from Algeria investigated various tea intakes during childhood and NPC among 72 cases and 72 controls matched for age, sex, and area of residence (Laouamri et al., 2001). No significant associations were reported between infusions or herbal teas with cumin (OR=1.35, 95% CI: 0.71-2.63), olive oil (OR=0.84, 95% CI: 0.34-1.97), fenu-greek (OR=2.0, 95% CI: 0.51-7.78), or aniseed (OR=1.66, 95% CI: 0.09-28.3) and risk NPC. Bay leaf tea administered to newborns at least 3 times a week for at least 1 month was significantly associated with NPC when compared to no intake (OR=3.0, 95% CI: 2.93-5.23). 3.6.2.1 Black tea No results found. 3.6.2.2 Green tea A3 Case-control studies (1) In a study that observed no differences with respect to the temperature or frequency of tea drinking, green tea exhibited a protective association with NPC compared to non-drinkers after adjusting for age and sex in a case-control study in China and Hong Kong (Geser et al., 1978).

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3.6.3 Maté No results found. 3.6.4 Other hot drinks No results found. 3.7 Alcoholic drinks A3 Case-control studies (1) In a U.S. case-control study that used beer drinkers as the referent category, drinking wine (OR=1.6, 95% CI: 0.4-6.4) or liquor (OR=0.9, 95% CI: 0.4-2.1) were not significantly associated with NPC risk after adjustments for age, sex, and smoking (Vaughan et al., 1996). 3.7.1 Total Alcoholic Drinks A2 Cohort studies (1) One historical cohort study from Sweden reported results for NPC incidence among alcoholics and non-alcoholics (Boffetta et al., 2001). After adjustment for age, sex, and calendar year, a standard incidence ratio of 1.56 (95% CI: 0.97-2.39) was reported for alcoholics when compared to non-alcoholics. A3 Case-control studies (18) A total of 18 case-control studies reported on the association between alcohol drinking and NPC. Eight of these studies reported data in sufficient detail to perform a dose-response meta-analysis. The results of the dose-response meta-analysis based on the number of alcohol drinks per week showed evidence of a trend of increasing NPC risk as alcohol drinking increased (summary random effects OR 1.01; 95% CI 1.00-1.03 per drink/week). B2 Size of effect The magnitude of the summary OR (summary random effects OR 1.01; 95% CI 1.00-1.03 per drink/week) observed in the dose-response meta-analyses is compatible with a dose-response association between alcohol drinking and NPC. Although the point estimate of the odds ratio appears small, considering the units of drink per week along with the possible range of drinks per week, the risk differential between heavier alcohol drinkers and non-drinkers is potentially large. B3 Biological Gradient The results of the dose-response analyses were compatible with a dose-response trend between alcohol drinking and NPC, with a summary random effect OR of 1.01 (95% CI 1.00-1.03 per drink/week). Of the eight studies that contributed evidence to the meta-analysis, six had odds ratios consistent with a dose-response relationship in the direction of increased risk. Of the remaining two studies, in one study the odds ratio was less than 1.0, in the other study the odds ratio equaled 1.0. In the studies with odds ratios greater than unity, the dose-response odds ratios equaled 1.02 in four studies, and were 1.06 and 1.14 in the other two studies.

Dose-Response Graph: Total Alcohol, Case-control studies

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B4 Internal Consistency/heterogeneity by dietary methodology A disconcerting feature of the evidence on the association between alcohol drinking and NPC is the lack of information reported in the papers on precisely how alcohol drinking was measured. Of the studies included in the dose-response meta-analyses, reports from five studies provided no description of the measurement tool. The remainder of the studies indicated use of study-specific FFQs or dietary history questionnaires. B5 Summary Illustrations of effects (e.g., forest plots)

Forest Plot for Dose-Response Analysis: Total Alcohol, Case-control studies

68

Odds Ratio, drinks/week .35 1 1.5

Study

Effect size

(95% CI) % Weight


NAS00612 (Taipei, Taiwan, Cheng, 1999) 1.06 ( 0.74, 1.53) 0.2

NAS00640 (US SEER, Nazar-Stewart, 1999) 1.02 ( 0.99, 1.06) 12.9

NAS00821 (Taiwan, Hildesheim, 1997) 0.99 ( 0.93, 1.05) 4.5

NAS00898 (US, Vaughan, 1996) 1.02 ( 1.00, 1.04) 18.6

NAS01254 (US Survey, Nam, 1992) 1.02 ( 1.00, 1.03) 23.9

NAS01495 (US-Washington, Vaughan, 1989) 1.02 ( 0.98, 1.07) 8.2

NAS01630 (Malaysia & Hong Kong, Yu, 1985) 1.14 ( 1.01, 1.29) 1.4

Overall 1.01 ( 1.00, 1.03) 100.0

Forest Plot for Highest vs. Lowest Analysis: Total Alcohol, Case-control studies

Odds Ratio: Highest vs. Lowest intake .05 1 9

Study

Effect size

(95% CI)


NAS00612 (Taipei City Taiwan, Cheng, 1999) 1.20 ( 0.68, 2.13)

NAS00640 (US SEER, Nazar-Stewart, 1999) 1.60 ( 0.82, 3.12)


NAS00898 (US, Vaughan, 1996) 2.00 ( 1.00, 4.00)

NAS01248 (Thailand, Sriamporn, 1992) 1.50 ( 0.68, 3.30)

NAS01254 (US Survey, Nam, 1992) 1.80 ( 1.07, 3.02)

NAS01410 (Taiwan, Chen, 1990) 1.84 ( 0.97, 3.48)

NAS01495 (US-Washington, Vaughan, 1989) 2.43 ( 0.67, 8.84)

NAS01630 (Malaysia & Hong Kong, Yu, 1985) 2.80 ( 1.18, 6.62)

B6 Gene-nutrient interactions In the study of Hildesheim et al, the potential interaction between GSTM1 and alcohol intake was evaluated. No statistically significant interaction was observed overall, but among the heavier drinkers those with the GSTM1 null genotype had a higher risk of NPC, an association that was stronger than among lighter drinkers. In analyses limited to squamous cell carcinoma, the interaction was of borderline statistical significance (p=0.06). C Assessment of heterogeneity within and between study types

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Within the case-control dose-response meta-analysis, statistically significant heterogeneity was detected, with an I2 statistic of 50%. The sources of heterogeneity appear to stem from the studies that observed no dose-response trend, particularly the most heavily weighted study included by Yuan et al, which observed a dose-response odds ratio of 1.0 (Yuan et al., 2000a). Also adding to the heterogeneity was the much less heavily weighted study with a dose-response odds ratio of 0.99 conducted in Taiwan (Hildesheim et al., 1997b). A study that was an outlier in the risk direction took place in Malaysia and Hong Kong with a dose-response OR of 1.14; this study contributed little weight to the overall meta-analyses (Yu et al., 1985). D. Factors influencing heterogeneity and meta-regression Unlike many of the other exposures included in this systematic review, for which the evidence emanates almost exclusively from geographic regions with high rates of NPC, the dose-response evidence for alcohol drinking includes four of eight studies from the United States. Furthermore, the evidence includes only one study from China, with two from Taiwan and one from Malaysia and Hong Kong. This variability in geographic regions is a potentially important source of variability, as the distribution of exposure to risk factors such as salted fish consumption would vary widely between these populations. An additionally important source of variability, but about which little is known, is the degree to which the measurement of alcohol drinking may have contributed to the heterogeneity. E. Important quality issues for interpretation of the evidence The dose-response meta-analyses for the case-control evidence for the association between alcohol drinking and NPC yielded results compatible with an increased risk associated with alcohol drinking. An important consideration is the potential confounding factors that have been accounted for in these studies. Of the eight studies, one was not adjusted for any factors. Seven of the studies adjusted for sex, and six adjusted for age. An important potential confounder for alcohol drinking is cigarette smoking, and four of the studies included adjustments for cigarette smoking. Other factors adjusted for in at least two studies included education, family history of NPC, and ethnicity. The study that adjusted for the most factors, and was the only study to include adjustments for dietary factors, was a study in China that observed no evidence of a dose-response trend (Yuan et al., 2000a). Given the fact the quantitative evidence favoring the presence of a dose-response trend is equivocal, the strength of evidence is further weakened by the fact that other dietary factors were not taken into consideration in the studies that provided evidence favoring a dose-response association. The absence of information on EBV infection status is particularly notable. The limited extent to which potential confounding variables have been controlled for, and the genuine potential for confounding to contribute importantly to the association between alcohol drinking and NPC, makes this an important issue affecting the quality of the overall evidence. Ten of the case-control studies could be included in highest-versus-lowest categories comparison. The results of this data summary are in keeping with the results of the dose-response meta-analysis, in that the evidence tends to point more strongly than not in favor of an association between alcohol drinking and NPC, but the evidence is not entirely consistent. Of the ten studies, only one reported an odds ratio of less than unity, whereas two studies reported odds ratios between 1.01 and 1.20, four studies reported odds ratios between 1.50 and 1.85, and three studies reported odds ratios of 2.0 or greater. Seven of the 17 case-control studies that reported information concerning the association between alcohol drinking and NPC did not present sufficient data to be included in any of the quantitative data summaries. In two case-control studies in China, one a study of alcohol habits among 205 NPC cases and 205 controls (Zheng et al., 1994a), and the other comparing alcoholic drinks among 88 cases and 176 controls (Zheng et al., 1994b), it was mentioned in the text that the case-control differences in alcohol drinking were “not significant.” There was no indication the results of these studies were adjusted for any factors. In a study of 120 cases and 120 controls among Chinese in Singapore, Shanmugaratnam et al reported an OR of 1.5 (“not significant”) for daily-

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versus-never alcohol drinking, after adjusting for age and sex (Shanmugaratnam et al., 1978). In a study with very little detail presented at all among Chinese in Malaysia, Armstrong et al noted no significant differences between cases and controls with respect to their measure of alcohol drinking (Armstrong et al., 1983b). In the United States, Mabuchi noted a lack of statistically significant difference between cases and controls for drinking one or more drinks per day compared to less than one drink per day (Mabuchi et al., 1985). Two additional studies carried out in China observed comparable levels of alcohol drinking in NPC cases compared to controls after adjusting for age, sex, and other factors (Ning et al., 1990, Zou, 1999). Because only minimal information about the results were presented, it is difficult to compare the results of these seven studies to the results of the studies that presented more thorough descriptions of the results and were included in the quantitative synthesis of the evidence. With this caveat, the results of these seven studies clearly seem to be less supportive of an association than studies included in the quantitative synthesis of the evidence. Added to the somewhat inconsistent findings of the studies included in the quantitative summaries of the evidence, the results of the studies not included in the quantitative review tend to further detract from the strength of evidence. In summary, the case-control evidence is equivocal, but the quantitative summaries of the evidence tend to suggest that alcohol drinking is associated with increased NPC risk. In addition to the lack of consistency in the evidence, the evidence is weak with respect to measurement of alcohol drinking, and the lack of careful control for confounding factors that could potentially account for much of the observed association, such as cigarette smoking. Furthermore, consideration of the reports not included in the quantitative data summaries, despite being having important limitations, tends to further weaken the overall evidence.

Funnel Plot for Dose-Response Analysis: Total Alcohol Intake, Case-control studies


logR


-.4

-.2

0

.2

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Funnel Plot for Highest vs. Lowest Analysis: Total Alcohol Intake, Case-control studies

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logR

s.e. of: logR0 .2 .4 .6 .8

-1

0

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2

F. Mechanisms and animal experimental data Based on the present analyses, ethanol intake was associated with only a small increased risk of NPC, but an association of alcohol intake with increased risk for other upper aerodigestive tumors makes this association plausible. Interactions between alcohol drinking and EBV have not been directly explored. A recent review summarizes the increased risk associated with esophageal and head and neck cancer, as well as possible mechanisms behind this association (Yokoyama et al., 2003). This positive influence may be attributed to the formation of acetaldehyde, an oxidized product of ethanol. Acetaldehyde is carcinogenic and mutagenic, binding to DNA and protein (Poschl et al., 2004). Ethanol is eliminated from the body by its oxidation, first to acetaldehyde and then to acetate. These reactions are sequentially catalyzed by alcohol dehydrogenase and aldehyde dehydrogenase. Most of the acetaldehyde generated during alcohol metabolism in vivo is promptly eliminated by aldehyde dehydrogenase-2 (ALDH2), the low-Km mitochondrial ALDH. However, a mutant form of ALDH2, ALDH2*2 allele (Glu487Lys) encodes a catalytically inactive protein. The inactive form of ALDH2 with the mutant ALDH2*2 allele is common in people of Japanese descent. The distribution of the ALDH2*2 allele varies by race, being prevalent in East Asians, but not in Caucasians or Africans. When this enzyme is inactive, the body fails to metabolize acetaldehyde rapidly, leading to excessive accumulation of acetaldehyde. Thus, genetic predisposition may amplify the toxic and mutagenic effects of alcohol consumption. While this effect has been primarily attributed to esophageal and head and neck cancer, it is possible that similar effects may occur in other upper aerodigestive tumors including NPC, as exposure to these tissues would be similar.

Chronic alcohol consumption also induces cytochrome P450 enzyme (CP2E1) activity in mucosal cells (Poschl et al., 2004). As discussed above, the resulting increased activation of various dietary and environmental carcinogens would increase the mutagenic effects of dietary nitrosamines. In addition, alcohol intake has been shown to affect folate levels (Giovannucci, 2002) through inhibition of folate absorbance and through increased excretion of folate by the kidneys. Resulting folate deficiency may contribute to the accumulation of additional genetic and epigenetic alterations, as discussed above. All of these effects may contribute to the increased risk of NPC potentially seen in patients with consumption of alcohol. 3.7.1.1 Beers A3 Case-control studies (3) Beer drinking was not associated with NPC risk in two case-control studies conducted in the U.S. (Henderson, 1976, Mabuchi et al., 1985). Henderson et al observed an odds ratio of unity (p=0.48) for any use of beer among 156 cases and 267 when adjusted for age, sex, area of residence, ethnicity/race, and socio-economic

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status. In the second US study, Mabuchi et al reported no significant association for the consumption of at least one ale-beer per day when adjusted for age, sex, ethnicity/race, and marital status. In a study conducted among Chinese in Malaysia, a significantly increased risk was observed with beer drinking (OR 1.3; p=0.02) after adjustments for salted fish intake and socioeconomic status (Armstrong et al., 1998b). 3.7.1.2 Wines A3 Case-control studies (4) Of the four case-control studies have reported on wine drinking and NPC, two were conducted in the U.S. (Henderson, 1976, Mabuchi et al., 1985) and two were conducted in China (Geser et al., 1978, Lin, 1973). Only one study actually reported a measure of association; this study was conducted in the U.S. and a protective association of borderline statistical significance (OR 0.7; 95% CL 0.4, 1.1) was observed (Henderson, 1976). Others simply reported findings as significant (Geser et al., 1978) or non-significant (Lin, 1973, Mabuchi et al., 1985) without details. 3.7.1.3 Spirits A3 Case-control studies (3) In a study of Chinese in Malaysia, a strong, positive trend was observed between drinking alcoholic spirits and NPC risk (p-for-trend 0.008) among 282 cases and 282 controls (Armstrong et al., 1998b). A slight, but not statistically significant was observed in an early U.S. study (OR=1.2, p=0.31) (Henderson, 1976), and in a more recent U.S. study the findings were reported as statistically significant but without details given (Mabuchi et al., 1985). A5 Ecological studies (1) In an ecologic study in the U.S., per capita consumption of alcoholic spirits was significantly correlated with NPC among men (r2=0.21, p<0.001), but not among women (r2=0.01, p>0.05), after group-level adjustments were made for age and race/ethnicity (Longnecker-M-P et al., 1981). 3.7.1.4 Other alcoholic drinks A3 Case-control studies (1) In a small study of 18 cases and 16 controls conducted in the U.S., drinking at least one mixed drink a day was not significantly associated with NPC risk when adjusted for age, sex, ethnicity and race, and marital status (Mabuchi et al., 1985). 4 Food production, preservation, processing and preparation 4.1 Production No results found. 4.1.1 Traditional methods (to include ‘organic’) No results found. 4.1.2 Chemical contaminants

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A3 Case-control studies (2) In a Chinese case-control study reported twice (Zheng et al., 1993, Zheng et al., 1994a), drinking of polluted water was reported to be statistically significantly associated with NPC, reported only in the text without detail. The authors went on to note, that after drinking polluted water was added to a conditional logistic regression model that also included salted fish, drinking polluted water was no longer statistically significantly associated with NPC. It is difficult to draw strong inferences without more details, but this description of the results suggests that the observed association between drinking polluted water and NPC may be due to positive confounding by salted fish consumption. 4.1.2.1 Pesticides No results found. 4.1.2.2 DDT No results found. 4.1.2.3 Herbicides No results found. 4.1.2.4 Fertilisers No results found. 4.1.2.5 Veterinary drugs No results found. 4.1.2.6 Other chemicals No results found. 4.1.2.6.1 Polychlorinated dibenzofurans (PCDFs) No results found. 4.1.2.6.2 Polychlorinated dibenzodioxins (PCDDs) No results found. 4.1.2.6.3 Polychlorinated biphenyls (PCBs) No results found. 4.1.2.7 Heavy metals

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No results found. 4.1.2.7.1 Cadmium A3 Case-control studies (2) Two case-control studies, both conducted in China, have explored the possible relationship between markers of cadmium exposure and NPC. Ling-Wei and colleagues, in a comparison of 45 NPC cases with 30 controls, observed that the median cadmium exposure in NPC cases was 740% greater than controls (p-value 0.01) (Deng, 1995, Ling-Wei et al., 1988). Deng and colleagues assessed cadmium exposure by measuring concentrations in serum, as well as in rice and drinking water. In the comparison of 44 NPC cases with 42 controls, mean serum cadmium concentrations were 48% higher in cases than controls (p-value <0.01), mean cadmium concentrations in rice were 38% higher in cases than controls (p-value <0.05), and mean cadmium concentrations in drinking water that were 20% higher in cases than controls (p-value >0.05) (Deng, 1995). The reported results are thus consistently in the direction of increased risk, but the inferences are limited due to small sample sizes and the fact that in none of these comparison were potentially confounding variables adjusted for. 4.1.2.7.2 Arsenic A3 Case-control studies (1) In a case-control study in China, the mean arsenic concentrations in hair samples were 47% higher (p-value <0.05) in NPC cases (n=22) compared to controls (n=56) (Man et al., 1996). No adjustments were made in the analyses. A5 Ecological studies (3) Three ecologic studies in China and Taiwan have evaluated the relationship between arsenic concentrations in drinking water and the rates of NPC occurrence (Chen et al., 1990, Tsai et al., 1999, Wu et al., 1989). None of these studies found a statistically significant association between area measures of arsenic drinking water concentrations and area-level rates of NPC. 4.1.2.7.3 Other heavy metals Lead A3 Case-control studies (3) Three case-control studies reported on the association between lead exposure and NPC. Lead was measured differently in each study, as the specific exposures were “lead in maize leaf,” “lead in drinking water,” and “lead detected in hair sample.” The study of lead concentrations in maize leaf, conducted in Kenya, the mean exposure of NPC cases was actually 3% less than in controls, a difference that was not statistically significant (Robinson et al., 1968). In a study in China, the mean drinking water concentrations of lead were 300% higher in NPC cases than controls, a difference that was statistically significant (Ling-Wei et al., 1988). The study of Man et al in China used an actual biomarker of lead exposure. In this study, the mean lead concentrations in hair samples were actually 25% lower in NPC cases than controls, a difference that was not statistically significant (Man et al., 1996). The heterogeneous findings observed may at least be partly a function of the different exposures that were measured in each study. Mercury A3 Case-control studies (1)

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One case-control study conducted in China assessed the association between mercury concentrations in hair samples and NPC. Mercury concentrations in hair samples were 25% higher in cases than controls (“not significant”), in an unadjusted comparison of 29 NPC cases with 95 controls (Man et al., 1996). Molybdenum A3 Case-control studies (2) Two case-control studies reported on the association between molybdenum exposure and NPC. Different measures of molybdenum were used. In a study in Kenya, the specific exposure investigated was “molybdenum in maize leaf.” In a study in China, three different molybdenum were investigated, concentrations in serum, concentrations in rice, and concentrations in drinking water. In the study of molybdenum concentrations in maize leaf, conducted in Kenya, the mean exposure of NPC cases was 13% higher than in controls, a difference that was not statistically significant (Robinson et al., 1968). In the study in China (Deng, 1995), measures of molybdenum exposure were 25% or more lower in cases than controls in serum, rice, and drinking water, differences all with p-values less than 0.05. The heterogeneous findings observed may at least be partly a function of the different exposures that were measured in each study or the different exposure levels in the two regions. Nickel A3 Case-control studies (2) Two case-control studies reported on the association between nickel exposure and NPC. Different measures of nickel were used. In a study in Kenya, the specific exposure investigated was “nickel in maize leaf.” In a study in China, three different nickel exposures were investigated, concentrations in serum, concentrations in rice, and concentrations in drinking water. In the study of nickel concentrations in maize leaf, conducted in Kenya, the mean exposure of NPC cases was 3% higher than in controls, a difference that was not statistically significant (Robinson et al., 1968). In the study in China (Deng, 1995), all three measures of nickel exposure were markedly higher in cases than controls. The mean exposure to nickel was higher in cases than control by 61% in serum, 26% in rice, and 62% in drinking water, differences all with p-values less than 0.05. The findings for nickel thus differ from those observed for lead and molybdenum in providing somewhat consistent evidence of increased risk. The relatively scant evidence, and the use of different exposures that were measured in each study or the different exposure levels in the two regions, are worth consider in assessing whether or not this evidence reflects a genuine association. 4.1.2.8 Waterborne residues No results found. 4.1.2.8.1 Chlorinated hydrocarbons No results found. 4.1.2.9 Other contaminants A3 Case-control studies (1)

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In a case-control study in China, nitrosamines from soybean products were not associated with increased risk of NPC, but the evidence suggested nitrosamines from other smoked foods were associated with NPC risk particularly if consumed during childhood (Ward et al., 2000). A5 Ecological studies (1) In an ecologic study carried out in the U.S, water fluoridation was observed to be statistically significantly positively correlated with NPC rates among both men and women (Takahashi et al., 2001). 4.2 Preservation Preserved animal foods Preserved meat: Adulthood consumption A3 Case-control studies (4) Four case control studies addressed the question of whether consumption of generally preserved meats in adults was associated with an increased risk of NPC. One study was carried out in Algeria (Laouamri et al., 2001), but the remaining three studies were conducted on Chinese populations in China (Yuan et al., 2000b, Zheng et al., 1994b) or Singapore (Lee et al., 1994). With the exception of Zheng et al, all authors at least adjusted for age and sex in the analysis. All studies used a food frequency questionnaire that was study specific. The cases included in each of the studies ranged from 72 to 935. The specific preserved meats between studies varied. One of the studies found no significant association between consumption of any of the preserved meat products and occurrence of NPC. The study of Zheng et al found no significant association between salted, dried and tinned meats as a group and NPC, but this study did not specify any details on the exposure range used to test significance, the odds ratio or whether any of the data were adjusted for any potential confounding variables. Three studies reported significant associations between exposure to preserved meats and NPC. Laouamri et al found a significant odds ratio of 4.75 associating consumption of dried or salted meat currently to 29 years ago after adjusting for age sex and area of residence. Yuan et al evaluated the risk associated with consumption of any preserved meat based on a frequency of consumption divided into 3 categories. The odds ratio was significant but low (1.77) as was the trend based on 935 cases and the data were adjusted for the usual variables as well as environmental factors and history of ear infection. The study of Lee et al evaluated the intake of rou gan and dried meat and found a significant association with NPC although the authors failed to provide any details such as the odds ratio. This is the only study that adjusted for other foods and vitamins as well as age, sex, ethnicity and education. The other foods for which the authors have adjusted may not actually be confounding factors or may be correlated with the dried meat intake. Preserved meat: Childhood consumption A3 Case-control studies (2) Two case control studies addressed risks of NPC from consumption of generally preserved meat in childhood. One study included Chinese subjects from Singapore and the other was done in Tunisia. Both used food frequency questionnaires to determine exposures. Both studies indicated no significant associations between consumption of preserved meats at various ages in childhood and the risk of NPC adjusted for age and sex and, for the Tunisian study, area and lifestyle factors as well (Jeannel et al., 1990a). The study of Lee et al in Singapore indicated no association between exposure to rou gan at age 10 and NPC with an odds ratio of 0.8

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and a borderline significant negative trend (p=0.08) using exposures at various frequencies per week and never consumed (Lee et al., 1994). Preserved fish (excluding salted fish) A2 Cohort studies (1) A cohort study of 505 men and women from China reported unadjusted associations for salted and dried fish consumption during different decades and NPC (Zou, 1994). Any consumption during the 1960’s, 1970’s, or 1980’s was reported as significantly associated when compared to no consumption (p<0.001 for all decades). A3 Case-control studies (1) One case-control study contributed evidence concerning intake of generally preserved fish and NPC. In the study by Lee et al, risks for various types of preserved fish were examined for different age groupings (Lee et al., 1994). Their only significant finding was for dried, unsalted fish consumed at age 10 (OR=0.1, 95% CI: 0.01-1.0). Other exposures they investigated included dried, tiny fish; dried, tiny fish soup; preserved cuttlefish; preserved fish tidbits; and fish gravy, but none were observed to be significantly associated with NPC at any age group. Preserved eggs A3 Case-control studies (3) Three case-control studies examined the risk of NPC associated with the consumption of generally preserved eggs. All studies included Chinese from either Singapore (Lee et al., 1994) or China. All used study-specific food frequency questionnaires to identify exposures. None of the studies indicated significant associations between the cancer and preserved eggs of any kind. The studies of Yuan et al and Lee et al adjusted the odds ratios for several demographic variables (Lee et al., 1994, Yuan et al., 2000b). These studies examined the risks from exposure to either unspecified types of preserved eggs or century eggs from exposures at age 10 and in adulthood. The odds ratios and the trends were not significant. The other study (Zheng et al., 1994b) did not specify the odds ratios but simply reported no significant associations between NPC and salted, dried and tinned eggs. Preserved fats A3 Case-control studies (1) One case-control study reported on the association between consumption of preserved fats and the risk of NPC. The study, carried out in Algeria, reported on the exposures of “dried, salted fat” in addition to a general measure of fat intake. A strong increased risk of NPC (OR 9.2; 95% CI 3.9-21.5) was noted with current consumption of dried, salted fat, after adjusting for age, sex, and neighborhood (Laouamri et al., 2001). In this same study population, the measure of fat intake also exhibited an association in the direction of increased risk that was less robust (OR 2.4; 95% CI 0.9-6.6). Preserved plant foods Total preserved vegetables: Adulthood consumption A3 Case-control studies (4) A total of 4 case-control studies reported results for total preserved vegetables and NPC. Ever-versus-never consumption of preserved vegetables was not significant in a Chinese study of 375 cases and 327 controls (Ward et al., 2000). A large Chinese study of 935 cases and 1032 controls by Yuan et al observed a significant

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association between preserved vegetable intake and NPC (OR=1.43, 95% CI: 1.11-1.86) (Yuan et al., 2000b). Lee et al also reported a significant association between canned, salted, or pickled vegetables and NPC (OR=4.9, CI: 1.8-12.9) (Lee et al., 1994). A study by Zheng et al, reported no significant association for salted, dried, or tinned vegetables in brine (Zheng et al., 1994b). Total preserved vegetables: Childhood/Infancy consumption A3 Case-control studies (2) Two case-control studies investigated preserved vegetables during childhood and risk of NPC. The first study by Ward et al matched cases and controls in China (Ward et al., 2000). Non-significant associations were reported for intake of preserved vegetables at age 10 (OR=0.9, 95% CI: 0.3-2.6), at age 3 (OR=0.9, 95% CI: 0.3-2.4), and during weaning (OR=1.3, 95% CI: 0.6-2.5). Consumption of canned, salted or pickled vegetables at age 10 was not observed to be associated with NPC (OR=0.5, 95% CI: 0.1-1.4) in a study of Chinese in Singapore as reported by Lee et al (Lee et al., 1994). Preserved Root Vegetables A3 Case-control studies (1) The association between generally preserved root vegetables and NPC was evaluated in a single case-control study. In the Chinese study, preserved root vegetables consumed at age 10 were positively associated with NPC (OR=1.81, 95% CI: 1.01-3.33) and other preserved root vegetables consumed during adulthood were positively associated with NPC (OR=2.42, 95% CI: 0.99-5.92) (Huang, 1997). Preserved Cruciferous Vegetables: Adulthood consumption A3 Case-control studies (2) Two studies reported results for preserved cruciferous vegetables consumed during adulthood. Both studies included Chinese men and women from Singapore or China. In the study by Lee et al, results for 3 types of preserved cruciferous vegetables were in the risk direction, but only 2 were significant (Lee et al., 1994). The 2 significant results were for preserved Chinese radish (OR=2.8, 95% CI: 1.2-6.0) and salted mustard greens (OR=3.1, 95% CI: 1.4-6.5). No significance was observed for preserved cabbage (OR=1.5, 95% CI: 0.6-3.4). Ning et al reported no significant association for sour cabbage (Ning et al., 1990). Preserved Cruciferous Vegetables: Childhood consumption A3 Case-control studies (2) Two studies focused on various preserved cruciferous vegetables and any age group below age 10 years, with 1 reporting estimates for odds ratios. Both studies assessed the association between types of preserved cabbage at age 10 and NPC. No significance was observed for preserved cabbage consumption at age 10 by Lee et al (OR=0.8, 95% CI: 0.2-2.6) or for sour cabbage at age 10 by Ning et al (Lee et al., 1994, Ning et al., 1990). Preserved radish was examined by Lee et al; an odds ratio of unity (95% CI: 0.4-2.1) was reported for consumption of preserved Chinese radish at age 10. Preserved Green Leafy Vegetables: Adulthood consumption A3 Case-control studies (1) One case-control study evaluated the association between generally preserved green leafy vegetables and NPC. The study of Chinese in Singapore reported a non-significant association between mei chye (preserved greens and leafy vegetables) and NPC after adjustment for various confounders (Lee et al., 1994).

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Total Preserved Vegetables: Adulthood consumption A3 Case-control studies (3) Three studies reported results for total preserved vegetables consumed during adulthood and NPC. In an Algerian study, 72 cases and 72 controls were matched by age, sex, and area of residence (Laouamri et al., 2001). This study observed vegetables in brine used as seasonings to be significantly related to NPC (OR=2.77, 95% CI: 1.34-5.71). A Chinese study by Yuan et al examined various types of preserved vegetables in a population of 935 cases and 1032 controls (Yuan et al., 2000b). They reported a significant risk for the consumption of preserved stem vegetables (OR=1.88, 95% CI: 1.24-2.84) and non-significant associations in the direction of risk for the consumption of preserved leafy vegetables (OR=1.37, 95% CI: 0.65-2.9) and preserved root vegetables (OR=1.04, 95% CI: 0.7-1.53). Mei chye, a dish of preserved greens and leafy vegetables, was shown to be in the direction of risk, but was not significant (OR=2.8, 95% CI: 0.9-8.2) in a study of Chinese in Singapore (Lee et al., 1994). Total Preserved Vegetables: Childhood consumption A3 Case-control studies (1) One study reported on generally preserved vegetables consumed during childhood. In the study of Chinese in Singapore (Lee et al., 1994), including 150 cases and 341 controls, intake of preserved greens and leafy vegetables was not significantly associated with NPC (OR=1.3, 95% CI: 0.6-2.6) when adjusting for age, sex, education level, and dialect group. Other Preserved Vegetables: Adulthood consumption A3 Case-control studies (2) Generally preserved vegetables consumed during adulthood was investigated in 2 case-control studies, both reported significant risk associations with NPC. An odds ratio of 7.5 (95% CI: 3.09-18.2) was reported for salted and dried tomatoes in an Algerian study which matched 72 cases and 72 controls by age, sex, and area of residence (Laouamri et al., 2001). Plum vegetable was shown as significantly associated with NPC (OR=2.53, 95% CI: 1.04-6.19) when maximally adjusted for in a Chinese study (Chen et al., 1997). Preserved fruits A3 Case-control studies (1) A study of Chinese in Malaysia including 282 cases and 282 controls investigated the association between consumption of preserved fruits at age 10 and 5 years prior to diagnosis and risk of NPC (Armstrong et al., 1998b). An unadjusted odds ratio of 1.42 (95% CI 0.71-2.85) was reported for those who consumed preserved fruit more than weekly 5 years prior to diagnosis compared to those with less than monthly consumption. More than weekly consumption at age 10 was not significantly associated with NPC when compared to less than monthly consumption (unadjusted OR=1.50, 95% CI 0.82-2.75). Preserved citrus fruits A3 Case-control studies (1) One study of 104 cases and 104 controls in China evaluated the association between preserved citrus fruits and NPC (Huang, 1997). Consumption of preserved citrus fruits at age 10 was reported as a risk factor for NPC when compared to no consumption (unadjusted OR=2.17, 95% CI 1.12-4.21). After adjustment for age, sex, no

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separate kitchen, intake of dried vegetables and grapes, and family history of cancer, an odds ratio of 2.95 (95% CI 1.04-8.41) was reported for consumption of preserved oranges when compared to no consumption. Preserved plums: Adulthood consumption A3 Case-control studies (4) Various types of preserved plums consumed during adulthood were examined in four case-control studies. All were in Chinese populations from China or Hong Kong. Yuan et al reported no significance for intakes of dried plums or preserved plums in a study of 935 cases and 1032 controls (Yuan et al., 2000b). Using maximally adjusted models, Chen et al reported significant risk results for the consumption of preserved prunes (OR=2.59, 95% CI: 1.04-8.41) and preserved plums (p-for-trend<0.05) in a matched case-control study (Chen et al., 1997). Limiting dietary intake to 3 years prior to diagnosis, Yu et al did not observe significant associations for 2 types of preserved, salted plums; however, when lifetime dietary data was used they observed significant associations for both types of salted plums (risk estimates not provided) (Yu et al., 1989). A second study by Yu et al reported non-significant results for preserved plums after adjusting for age, sex, and salted fish intake (Yu et al., 1986). Preserved plums: Childhood consumption A3 Case-control studies (4) Four studies investigated the relationship between consumption of preserved plums at age 10 and NPC risk. All studies were in Chinese populations from China or Hong Kong. Chen et al reported significant risk associations for preserved prunes (OR=2.17, 95% CI: 1.12-4.21) and preserved plums (OR=2.10, 95% CI: 1.12-3.91) using logistic regression analyses and matched cases and controls (Chen et al., 1997). Significant risk trends were observed by Yu et al for 2 types of preserved, salted plums (p-for-trends 0.01 and 0.03) after adjusting for age, sex, area of residence, and consumption of salted fish during weaning (Yu et al., 1989). A previous study by Yu et al did not observe associations for various preserved plums (Yu et al., 1986). The fourth study included 104 cases and 104 matched controls and reported a significant risk association for ever-versus-never intake of preserved plums at age 10 (OR=2.10, 95% CI: 1.12-3.91) (Huang, 1997). Preserved olives: Adulthood consumption A3 Case-control studies (1) One case-control study evaluated the relationship between generally preserved olives consumed during adulthood and NPC. A study of 72 cases and 72 matched controls in Algeria reported significant associations between consumption of olives in brine (OR=2.0, 95% CI: 1.36-3.72) and risk of NPC (Laouamri et al., 2001). Preserved spice intake A3 Case-control studies (3) Three case-control studies examined the risk of NPC and exposure to preserved spices. Laouamri et al studied Algerians and the other studies included Chinese from China or Hong Kong. Two studies used study-specific food frequency questionnaires and the other used dietary recall (Ward et al., 2000). The only significant positive association was from the Algerian study which evaluated harissa and showed an adjusted odds ratio of 5.0 (p<0.001) (Laouamri et al., 2001). The number of cases included in this study was 72. The study of Ward et al also reported no association of cancer with direct consumption of hot chili sauce. Geser et al found protective associations for household consumption of mustard paste (OR=0.44, 95% CI: 0.26-0.74) and chili sauce (OR=0.41, 95% CI: 0.24-0.69) (Geser et al., 1978).

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4.2.1 Drying Dried animal food Dried fish (excluding salted fish) A3 Case-control studies (4) Four case-control studies contributed evidence concerning intake of non-salted fish and NPC. Several of these studies only reported non-significant associations in the text without details (Ning et al., 1990, Yu et al., 1988). In a study by Lee et al, risks for various types of preserved fish were examined for different age groupings (Lee et al., 1994). Their only significant finding was for dried, unsalted fish consumed at age 10 (OR=0.1, 95% CI: 0.01-1.0). Other exposures they investigated included dried, tiny fish and dried, tiny fish soup, but none were observed to be significantly associated with NPC at any age group. Yu et al reported that consumption of dried fish was observed to be a significant risk factor when consumed at age 10 (OR=6.4, 95% CI: 1.6-26.8), but not at ages 1-2 (OR=2.2, 95% CI: 0.9-5.3). Dried anchovies, consumed during adulthood or at age 10, were not associated with NPC in another Chinese study by Ning et al. The fourth study by Armstrong et al examined the relationship between dried fish consumed during meals and NPC among Chinese in Malaysia (Armstrong, 1978). A significant association was reported when dried fish was consumed at breakfast, but no direction or estimate of risk was offered. When consumed in 3 daily meals, no association between dried fish and NPC was observed. Dried seafood: Adulthood consumption A3 Case-control studies (3) Three case-control studies examined the association between NPC and consumption of dried seafood. All studies evaluated exposures through the use of study-specific food frequency questionnaires. All studies included Chinese cases and controls. None of the studies showed significant odds ratios or trends with the different foods although all that reported odds ratios were in the positive direction. Lee et al studied the association between dried oysters and dried prawns and found no significant association after adjustment for basic variables (Lee et al., 1994). An earlier study of Yu et al examined the risks of eating dried shrimp both in childhood and 3 years prior to diagnosis and found no association after adjustment for possible confounding variables (Yu et al., 1986). Ning et al studied the intake of dried shrimp and found no significant association in the adjusted odds ratios (Ning et al., 1990). Dried seafood: Childhood consumption A3 Case-control studies (4) Three of the studies investigating adult consumption and one additional study by Yu 1988 examined the risks of NPC associated with eating of dried seafood in childhood. All studies examined exposure through the use of a study-specific food frequency questionnaire. All of the studies adjusted for at least age and sex in some of the analyses. All exposures examined showed no association with NPC and exposure in childhood. Lee et al examined consumption of dried prawns and dried oysters and found no association with exposure at age 10 to either food (Lee et al., 1994). Yu 1988 and 1986 and Ning et al examined the risks associated with consumption of dried shrimp at age 10 and combined with adult exposure and found no association even after adjustment for basic variables (Ning et al., 1990, Yu et al., 1986, Yu et al., 1988). Dried plant foods Dried vegetables: Adulthood consumption

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A3 Case-control studies (1) A single case-control study reported results for dried vegetables and NPC. In a study of 100 cases and 300 matched controls conducted in China, no significant associations were reported for dried vegetables (Ning et al., 1990). Dried vegetables: Childhood/Infancy consumption A3 Case-control studies (1) A single case-control study investigated dried vegetables during childhood and risk of NPC. Ning et al observed no significant associations for dried vegetables at age 10 (Ning et al., 1990). Dried Green Leafy Vegetables: Adulthood consumption A3 Case-control studies (1) A single case-control study evaluated the association between dried green leafy vegetables and NPC. A study of Chinese in China reported non-significant associations between dried kelp and dried seaweed and NPC after adjusting for age, sex, and area of residence (Ning et al., 1990). Dried Green Leafy Vegetables: Childhood consumption A3 Case-control studies (1) A single case-control study evaluated the association between dried green leafy vegetables consumed during childhood and NPC. A study of Chinese in China reported non-significant associations between consumption of dried kelp at age 10 and consumption of dried seaweed at age 10 and NPC after adjusting for age, sex, and area of residence (Ning et al., 1990). Dried plums: Adulthood consumption A3 Case-control studies (1) Dried plums consumed during adulthood were examined in one case-control study. Yuan et al reported no significance for intakes of dried plums in a study of 935 cases and 1032 controls (Yuan et al., 2000b). Dried plums: Childhood consumption A3 Case-control studies (1) One study investigated the relationship between consumption of dried plums at age 10 and NPC risk. A study by Yu et al did not observe associations for various dried plums (Yu et al., 1988). Dried olives: Adulthood consumption A3 Case-control studies (1) One case-control study evaluated the relationship between dried olives consumed during adulthood and NPC. A study of 72 cases and 72 matched controls in Algeria reported significant associations between consumption of dried olives (OR=4.66, 95% CI: 1.51-14.33) and risk of NPC (Laouamri et al., 2001). Other dried fruits: Adulthood consumption A3 Case-control studies (3)

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Three case control studies measured the association between dried fruits consumed during adulthood and NPC. One study of 72 cases and 72 matched controls in Algeria reported an odds ratio of 0.2 (95% CI: 0.08-0.17) for consumption of raisins (Laouamri et al., 2001). Two studies, one conducted in China and the other in Hong Kong, reported non-significant associations between dried red dates and NPC (Yu et al., 1986, Yuan et al., 2000b). Other dried fruits: Childhood consumption A3 Case-control studies (2) Two case control studies measured the association between dried red dates consumed at age 10 and NPC. One study was conducted in China and included 128 cases and 174 controls (Yu et al., 1988). The other study took place in Hong Kong and included 250 cases and 250 controls (Yu et al., 1986). Both reported non-significant associations between dried red dates and NPC and provided no other details. Dried seeds: Adulthood consumption A3 Case-control studies (1) One case-control study reported on the association between adulthood consumption of dried seeds and the risk of NPC. This study only mentioned in the text that the consumption of dried ginko seeds was not statistically significantly associated with NPC (Yuan et al., 2000b). Dried seeds: Childhood consumption A3 Case-control studies (1) One case-control study reported on the association between childhood consumption of dried seeds and the risk of NPC. In the Chinese study, the evidence presented was limited to mentioning in the text that the consumption of dried ginko seeds at age 10 years was not statistically significantly associated with NPC (Yu et al., 1988). Dried spice intake A3 Case-control studies (1) One case-control study examined the risk of NPC and exposure to dried spices. Laouamri et al studied Algerians and used a study-specific food frequency questionnaire (Laouamri et al., 2001). A significant positive association was observed for the intake of dried peppers (OR=5.5, 95% CI: 2.55-11.8). The number of cases included in this study was 72 and the range of case size for all studies was 60 to 375. 4.2.2 Storage A3 Case-control studies (1) In a case-control study in Algeria, Laouamri and colleagues investigated whether NPC risk might be related to the practice of feeding infants who are teething cherchem, wheat and barley pieces that are softened in underground storage when they come into contact with moist floors and walls. The comparisons were limited by the fact that this storage variable was measured as ever-versus-never consumption and the problem of remote recall of an infant feeding practice. The odds ratio for NPC was in the direction of increased risk (OR 4.0; 95% CL 0.18, 4.4) (Laouamri et al., 2001) [Technical note: the results are accurate as presented, but some error in reporting occurred because the confidence limits are not consistent with the point estimate of the OR]. 4.2.2.1 Mycotoxins

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No results found. 4.2.2.1.1 Aflatoxins No results found. 4.2.2.1.2 Others No results found. 4.2.3 Bottling, canning, vacuum packing A3 Case-control studies (1) After adjusting for age and sex, the relative odds of living in a household that consumed tinned foods with fish was significantly lower in cases than controls (OR 0.5; 95% CI 0.2-0.9) in a case-control study in China and Hong Kong (Geser et al., 1978). 4.2.4 Refrigeration No results found. 4.2.5 Salt, salting No results found. 4.2.5.1 Salt A3 Case-control studies (2) Two case-control studies have investigated whether consumption of table salt is associated with NPC. Both studies were conducted in China, by Yu and colleagues, and included adjustments for at least age and sex. These findings are of particular interest to this SLR because of the associations noted with salted foods, as they provide the opportunity to assess the potential independent influence of salt per se. In these studies, the results were not presented in detail but it was noted that there were no significant case-control differences for table salt consumed three years prior to diagnosis or at age 10 years (Yu et al., 1989, Yu et al., 1988). 4.2.5.2 Salting No results found. 4.2.5.3 Salted foods A3 Case-control studies (1) In a study conducted in the U.S., cases were significantly less likely than controls (OR 0.4; p=0.03) to have consumed salted snacks, after adjusting for age, sex, area of residence, and race/ethnicity (Henderson, 1976). 4.2.5.3.1 Salted animal food (excluding salted fish)

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Salted meat: Adulthood consumption A3 Case-control studies (1) One case control study addressed the question of whether consumption of salted meats in adults was associated with an increased risk of NPC. Ning et al examined consumption of salted meats and found no significant association with these foods and NPC (Ning et al., 1990). However, the exposure range tested was not specified and there was no information regarding whether any of the analyses were adjusted for possible confounders. Salted meat: Childhood consumption A3 Case-control studies (1) One case control study addressed risks of NPC from consumption of salted meat in childhood. The study by Ning et al examined exposures to salted meats at age 10 and salted meats three years before cancer diagnosis and indicated non-significant associations for all measures without any further details (Ning et al., 1990). Salted pork A3 Case-control studies (3) Three case-control studies, all implemented in China, reported on the association between salted pork consumption and NPC. The studies ranged in size from 128 cases/174 controls to 250 cases/250 controls, and all used study-specific food frequency questionnaires to measure the dietary exposure. None of the studies reported measures of association, but rather only whether the results were “statistically significant” or not. The one study to report a significant increased NPC risk was for the exposure of “salted pork” (Zheng et al., 1993). Consumption of salted pork or pork sausage at age 10 years or as an adult was reported to be not significantly associated with NPC risk in two other studies (Yu et al., 1986, Yu et al., 1988). Salted seafood: Adulthood consumption A3 Case-control studies (3) Three case-control studies examined the association between NPC and consumption of salted seafood. All studies evaluated exposures through the use of study-specific food frequency questionnaires. All studies included Chinese cases and controls. None of the studies showed significant odds ratios or trends with the different foods although all that reported odds ratios were in the positive direction. Yuan et al examined the association of intake of salted food pastes using 935 controls and found a non-significant association (odds ratio 1.44 p=0.07) after adjustment for age, sex, education and other lifestyle and environmental factors (Yuan et al., 2000b). Yu et al studied the association of consumption of salted fish paste at 3 years prior to diagnosis and at an unknown time and found no association after adjustment for basic variables as well as other suspect foods (Yu et al., 1989). Ning et al studied the intake of salted shrimp paste and found no significant associations in the adjusted odds ratios (Ning et al., 1990). Salted seafood: Childhood consumption A3 Case-control studies (2) Two studies examined the risks of NPC associated with eating of salted seafood in childhood. Both studies examined exposure through the use of a study-specific food frequency questionnaire. When Yu et al and Ning et al examined the risks of NPC associated with the consumption of salted shrimp paste at age 10 both authors reported a significant association either as a trend (Yu et al) or as an odds ratio (OR = 3.2 p=0.007) with adjustments for not only the basic variables but for others such as salted fish consumption (Ning et al., 1990, Yu

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et al., 1989). Yu et al also reported a borderline significant trend (0.07) for this exposure at the ages of 1-2 years in children. Salted eggs: Adulthood consumption A3 Case-control studies (5) Five case–control studies examined the risk of NPC associated with the consumption of salted eggs with conflicting results; however, only 3 provided the necessary data for a meta-analysis. All studies were conducted in Chinese but the Armstrong et al studies were done in Malaysia and the others in China. Lee et al and Ning et al used a food frequency questionnaire and examined either the intake of unspecified salted eggs in adulthood or intake of specific chicken or duck eggs three years before diagnosis and found no significant association (Lee et al., 1994, Ning et al., 1990). Armstrong et al examined the risk of family consumption of salted eggs at meals and reported no association (Armstrong, 1978). However, a later study by Armstrong showed a significant association and trend from consumption of salted eggs with exposure derived from a dietary history and adjustment for several other food variables (Armstrong et al., 1998b). The crude odds ratio of 2.55 and the trend were significant and the odds ratio remained significant but lower after adjustment for various foods. The adjusted ratio from the Ward et al study was similar using exposure data from a dietary questionnaire (OR= 2.00) (Ward et al., 2000). Salted eggs: Childhood consumption A3 Case-control studies (4) Four case-control studies examined the risks of NPC associated with the consumption of salted eggs in childhood. All studies were done in Chinese but the studies of Armstrong et al and Lee et al were done in Malaysia and Singapore respectively (Armstrong et al., 1998b, Lee et al., 1994). All studies determined the exposure based on a study-specific food frequency questionnaire except for the study of Armstrong et al that used a dietary history questionnaire. The Armstrong study of 282 cases examined the risks at age 10 and found a significant odds ratio without adjustment as well as an association between NPC and lifetime exposures to salted eggs at both age 10 and 5 years prior to diagnosis after adjustment for basic variables and other foods (OR = 1.24). Yu et al studied the risks of exposure to salted eggs at weaning in 128 cases and found a borderline significant association (OR= 5.0 CI 1.2-21) following adjustment with very wide confidence intervals (Yu et al., 1988). The studies of Lee et al and Ning et al with 149 and 100 cases respectively found no association from exposure to salted eggs at age 10 (Lee et al., 1994, Ning et al., 1990). 4.2.5.3.1.1 Salted fish Salted fish: Adulthood consumption A2 Cohort studies (1) One cohort study reported on the association between salted fish intake and NPC (Zou, 1994). This study was carried out in Sihui County, Guangdong Province, China. The cohort for the analyses of adulthood consumption of salted fish was based on 505 individuals between the ages of 35-64 years who were followed-up for nine years. During follow-up, 17 cohort members were diagnosed with NPC. The investigators queried about salted fish intake during the decades of the 1960s, 1970s, and 1980s. The results were all unadjusted; no measures of association were presented, with only p-values reported in the text. The p-values comparing salted fish intake at least once per week compared to less frequent consumption were <0.001, 0.014, and 0.21 for consumption in the 1960s, 1970s, and 1980s, respectively. It is difficult to make strong inferences based on small number of NPC cases and the limited information presented, but the results of this cohort study document

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the temporal association between salted fish intake and NPC risk and suggest that accounting for a longer latency period may strengthen the association between salted fish intake and NPC risk. A3 Case-control studies (21) A total of 21 case-control studies reported on the association between salted fish intake during adulthood and NPC. Nine of these studies reported data in sufficient detail to perform a dose-response meta-analysis. The results of the dose-response meta-analysis based on the number of times salted fish was consumed per week during adulthood showed evidence of a strong trend of increasing NPC risk as salted fish intake increased (summary random effects RR 1.28; 95% CI 1.13-1.44 per time/week). B2 Size of effect The magnitude of the summary RR (summary random effects RR 1.28; 95% CI 1.13-1.44 per time/week) observed in the dose-response meta-analyses indicates a strong dose-response association between salted fish intake and NPC. B3 Biological Gradient The dose-response analyses are compatible with a strong dose-response trend between salted fish consumption and NPC, with a summary random effect RRs of 1.28 (95% CI 1.13-1.44 per time/week). The results from all nine of the studies that contributed evidence to the meta-analysis were consistently in the direction of increased risk, with dose-response ORs ranging from 1.06 to 2.50 per time/week. There were three studies each with OR point estimates of 1.06 to 1.20, 1.21-1.50, and >1.50.

Dose-Response Graph: Salted fish intake during adulthood, Case-control studies

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B4 Internal Consistency/heterogeneity by dietary methodology In these studies, salted fish intake was measured using study specific FFQs or dietary history questionnaires, and was most often referred to as salted fish. All of the studies were hospital-based for case ascertainment. B5 Summary Illustrations of effects (e.g., forest plots)

Forest Plot for Dose-Response Analysis: Salted fish intake during adulthood, Case-control studies

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Study

Effect size

(95% CI) % Weight




NAS01248 (Thailand, Sriamporn, 1992) 1.35 ( 1.06, 1.72) 11.1


NAS01608 (Hong Kong, Yu, 1986) 1.31 ( 1.13, 1.51) 15.7

NAS06003 (S. Fujian China, Ye, 1995) 1.71 ( 1.08, 2.70) 5.2

NAS06010 (Fujian China, Cai, 1996) 1.06 ( 1.00, 1.12) 19.3

NAS06023 (Yangjiang China, Zou, 1999) 1.32 ( 1.13, 1.54) 15.2

Overall 1.28 ( 1.13, 1.44) 100.0

Forest Plot for Highest vs. Lowest Analysis: Salted fish intake during adulthood, Case-control studies


.01 1 100

Study Effect size (95% CI)







NAS01153 (Rizal Phillipines, West, 1993) 1.30 ( 0.67, 2.52)

NAS01248 (Northeast Thailand, Sriamporn, 1992) 2.50 ( 1.20, 5.20)


NAS01608 (Hong Kong, Yu, 1986) 7.50 ( 0.88, 63.89)


NAS06003 (South Fujian China, Ye, 1995) 5.00 ( 1.27, 19.72)

NAS06009 (Minan Fujian China, Ye, 1995) 2.00 ( 0.88, 4.56)

NAS06010 (Fujian China, Cai, 1996) 1.32 ( 0.98, 1.77)

NAS06021 (Guangxi China, Chen, 1994) 5.51 ( 1.74, 17.44)

NAS06022 (Heilongjiang China, Wang, 1993) 8.99 ( 1.60, 50.44)

NAS06023 (Yangjiang China, Zou, 1999) 3.07 ( 1.66, 5.69)

B6 Gene-nutrient interactions Does not apply.

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C Assessment of heterogeneity within and between study types Within the case-control dose-response meta-analysis, statistically significant heterogeneity was detected, with an I2 statistics of 75%. Inspection of the data reveals that the heterogeneity present relates to the magnitude of the dose-response gradient, not heterogeneity with respect to the presence of a dose-response trend. The results for all nine studies supported the presence of a positive dose-response trend. The source of the heterogeneity may relate to the fact that the two studies with the largest weights also observed the weakest dose-response trends, whereas studies with the smallest weights in the meta-analysis tended to observe strong dose-response trends. D. Factors influencing heterogeneity and meta-regression A factor that could contribute to the variability in the observed magnitude of associations is between-region differences in specific methods of salted fish preparation, and possibly with the type of fish consumed. This could potentially lead to differences in the risk associated with salted fish consumption but this is difficult to rigorously assess with so few studies, leaving an insufficient number of studies per region to analyze separately. E. Important quality issues for interpretation of the evidence The dose-response meta-analyses for case-control evidence for the association between salted fish intake and NPC yielded results compatible with a strong increased risk associated with salted fish intake. An important consideration is the potential confounding factors that have been accounted for in these studies. All nine of these studies included adjustments for at least age and sex, and the majority also controlled for neighborhood of residence. Other factors considered included cigarette smoking (3 studies), alcohol drinking (2 studies), and exposure to other environmental exposures (2 studies). Importantly, other dietary factors were rarely taken into consideration (1 study adjusted for consumption of fermented soy). The absence of information on EBV infection status is particularly notable. The limited extent to which potential confounding variables have been controlled for is thus an important issue affecting the quality of the overall evidence. Seventeen of the case-control studies could be included in highest-versus-lowest categories comparison. The results of this data summary strongly reinforce the evidence suggesting salted fish intake increases the risk of NPC. Of the 17 studies, only one reported an odds ratio of less than unity, whereas four studies reported odds ratios between 1.33 and 1.99, four studies reported odds ratios between 2.0 and 4.0, and in 8 studies odds ratios of greater than 4.0 were observed. Four of the 21 case-control studies that reported information concerning the association between adulthood consumption of salted fish and NPC did not present sufficient data to be included in any of the quantitative data summaries. In a case-control study of 205 NPC cases and 205 controls carried out in China, Zheng et al reported in the text that cases were “significantly” more likely to have the highest salted fish consumption, without reporting a p-value or measure of association (Zheng et al., 1993). In a study in Malaysia comprised of 100 NPC cases and 100 controls, the case-control difference in current salted fish consumption in adults was reported to be not statistically significantly different (Armstrong et al., 1983a). No measure of association or p-value was reported, but the comparison was adjusted for age, sex, area of residence, and ethnicity. Similar results to this were reported in a case-control study conducted in the U.S. (n=156 cases, n=267 controls) (Henderson, 1976). In a much larger study carried out in Taiwan, a comparison of the consumption of moldy and firm salted fish was reported to be not statistically significantly different between 502 NPC cases and 1942 controls (Yang, 2005). Because only minimal information about the results were presented, it is difficult to compare these four studies to those that presented more thorough descriptions of the results. With this caveat, the results of these four studies appear to be less supportive of an association than studies included in the quantitative synthesis of the evidence.

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In summary, the case-control evidence is clear and consistent in suggesting that salted fish intake is associated with increased NPC risk. The evidence to specifically pinpoint the observed risks to salted fish would be more convincing if potential confounding factors had been more completely accounted for.

Funnel Plot for Dose-Response Analysis: Salted fish intake during adulthood, Case-control studies


logR

s.e. of: logR0 .2 .4 .6

-1

-.5

0

.5

1

Funnel Plot for Highest vs. Lowest Analysis: Salted fish intake during adulthood, Case-control studies


logR

s.e. of: logR0 .5 1 1.5

-2

0

2

4

F. Mechanisms and animal experimental data More studies have examined the role of nitrosamines and nitrites in salted fish as essential agents for transformation of NPC precursor tissues. Evidence suggests that high intake of nitrate and nitrosamine from salted fish account for some of this increased risk of NPC development. Nitrosamines are known mutagens and animal carcinogens that induce gene mutation through the formation of DNA adducts which if not repaired may lead to point mutations. The N-nitrosamines are a large group of compounds with a common carcinogenic mechanism (Goldman et al., 2003). Salted fish has been shown to contain N-dimethylnitrosamine, N-diethylnitrosamine, N-nitrosopyrrolidene and N-nitrosopiperidine (Zou et al., 1992, Zou et al., 1994). Levels of these compounds were highest in salted fish from areas with the highest NPC mortality, while lower in areas

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with lower NPC mortality (Zou et al., 1992, Zou et al., 1994). Exposure of the nasopharynx to these agents may be particularly damaging in that the carcinogenic properties of nitrosamines are greatest following oral administration. In addition, the variation in nitrosamine content of salted fish may contribute to heterogeneity in assigning risk to salted fish consumption in different geographic locations.

Alkylating agents including nitrosamines produce DNA adducts, specifically 7-methylguanine and O6-methylguanine. The O6-methylguanine is mostly responsible for the mutagenicity and carcinogenicity of these alkylating agents (Goldman et al., 2003). Unfortunately, the genes targeted for mutational alteration in NPC have to a large degree not been identified, which does not allow a definitive association of nitrosamine exposure to tumor suppressor or oncogene mutation. Among the commonly mutated genes in other types of tumors, no reports describe mutation of k-ras and studies of mutation of the retinoblastoma gene (Lin et al., 1992, Sun et al., 1993) and p16/ CDKN2a (Lo et al., 1995, Sun et al., 1995) have all been negative. The most extensively studied gene in NPC for mutational alterations is p53, also the most commonly mutated gene in other malignancies. Ten published studies in the last 12 years have reported mutation of p53 ranging from 0-27% of NPC tumors studied (Burgos, 2003, Chakrani et al., 1995, Effert et al., 1992, Lo et al., 1992, Lung et al., 1998, Nasrin et al., 1994, Spruck et al., 1992, Sun et al., 1992, Van Tornout et al., 1997, Xie et al., 1997), with the 27% result in a study of only 11 tumors (Lung et al., 1998). Overall, 18 of 282 tumors have been found to contain p53 mutations (overall percentage 6%), suggesting that mutations in p53 are not common and do not provide a connection between nitrosamines and the progression of NPC. However, in at least one study (Van Tornout et al., 1997), all 4 of the mutations detected were GC>AT, of particular mechanistic importance for alkylating agents.

The O6-methylguanine leads to GC->AT transitions in cell-culture and animal models if not repaired by O6-methylguanine methyltransferase (MGMT), and as described above, this lesion is produced by alkylating agents. MGMT has been shown to be altered in NPC, although through epigenetic changes, rather than mutational inactivation. Hypermethyaltion of the promoter region of MGMT silences expression of this gene in many cancers (Esteller et al., 1999) which has been reported in 20-28% of nasopharyngeal cancer (Kwong et al., 2002, Wong et al., 2003). Inactivation of MGMT has been shown to be associated with the type of p53 mutations described above in lung and colon cancer (Esteller et al., 2001, Wolf et al., 2001), but due to the infrequent mutations in NPC has not been studied . As noted above, LMP-1 produced by EBV reactivation may also reduce DNA repair capacity, compounding the mutagenic effects of nitrosamine compounds.

Additional support for the importance of nitrosamines in the carcinogenic process of NPC is provided by studies examining the cytochrome p450 enzyme CYP2E1. N-nitrosodimethylamine undergoes enzymatic hydroxylation catalyzed mainly by CYP2E1, a step in the activation of carcinogenic adducts (Goldman et al., 2003). CYP2E1 is expressed in the nasopharynx and in NPC tumors (He et al., 2002). Increased activity of this enzyme would then result in increased activation of pro-carcinogens. A genetic polymorphism in the 5'-flanking region of the human CYP2E1, the C2 allele, affects binding of trans-acting factor to the promoter (Hayashi et al., 1991), This sequence change affects transcriptional regulation, resulting in up to 10-fold differences in promoter activity of the CYP2E1 gene (Hayashi et al., 1991). Studies have demonstrated an increased risk of developing NPC in patients with this variant form(Hildesheim et al., 1997a, Hildesheim et al., 1995, Kongruttanachok et al., 2001), (relative risks of 2-2.5, higher in non-smokers), consistent with the increased formation of carcinogenic nitrosamines from salted fish for those individuals. These studies suggest genetic modifiers of environmental exposure contribute to the risks inherent in consumption of salted fish. Such genetic variation may contribute to the heterogeneity in studies examining risk of NPC following salted fish consumption. Salted fish: Childhood consumption (Age 10)

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A3 Case-control studies (16) A total of 16 case-control studies reported on the association between salted fish intake at approximately 10 years of age and NPC. Nine of these studies reported data in sufficient detail to be included in a dose-response meta-analysis. The results of the dose-response meta-analysis based on the number of times salted fish was consumed per week when 10 years-old showed evidence of a strong trend of increasing NPC risk as salted fish intake increased (summary random effects RR 1.35; 95% CI 1.14-1.60 per time/week). B2 Size of effect The magnitude of the summary RR (summary random effects RR 1.35; 95% CI 1.14-1.60 per time/week) observed in the dose-response meta-analyses indicates a strong dose-response association between salted fish intake at age 10 years and NPC. B3 Biological Gradient The dose-response analyses are compatible with a strong dose-response trend between salted fish consumption and NPC, with a summary random effect RR of 1.35 (95% CI 1.14-1.60 per time/week). The results from eight of the nine studies that contributed evidence to the meta-analysis were in the direction of increased risk, with dose-response ORs ranging from 0.97 to 1.75 per time/week. There were three studies with OR point estimates of 1.10 to 1.20, one study with an OR between 1.21-1.50, and four studies with ORs between 1.51 and 1.75.

Dose-Response Graph: Salted fish intake at age 10, Case-control studies

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B4 Internal Consistency/heterogeneity by dietary methodology In these studies, salted fish intake was measured using study specific FFQs or dietary history questionnaires. All of the studies were hospital-based for case ascertainment. B5 Summary Illustrations of effects (e.g., forest plots)

Forest Plot for Dose-Response Analysis: Salted fish intake at age 10, Case-control studies

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Study

Effect size

(95% CI) % Weight






NAS01608 (Hong Kong, Yu, 1986) 1.74 ( 1.40, 2.16) 12.2

NAS01712 (Selangor Malaysia, Armstrong, 1983) 1.51 ( 1.17, 1.96) 11.3

NAS01922 (Tianjin City China, Ning, 1990) 1.55 ( 1.18, 2.04) 11.0

NAS05679 (Taiwan, Yang, 2005) 1.18 ( 0.91, 1.53) 11.3

Overall 1.35 ( 1.14, 1.60) 100.0

Forest Plot for Highest vs. Lowest Analysis: Salted fish intake at age 10, Case-control studies


.01 1 100

Study

Effect size

(95% CI)









NAS01608 (Hong Kong, Yu, 1986) 37.70 ( 14.12, 100.65)


NAS01766 (Alaska US, Lanier, 1980) 4.00 ( 0.57, 28.06)


NAS05679 (Taiwan, Yang, 2005) 1.78 ( 0.82, 3.88)

NAS06020 (Heilongjiang China, Na, 1988) 5.50 ( 0.99, 30.62)

B6 Gene-nutrient interactions Does not apply. C Assessment of heterogeneity within and between study types

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Within the case-control dose-response meta-analysis, statistically significant heterogeneity was detected, with an I2 statistics of 83%. The presence of a dose-response trend was observed so consistently that the heterogeneity present relates primarily to the magnitude of the dose-response gradient, not with respect to the presence or absence of a dose-response trend. The results for eight of nine studies supported the presence of a positive dose-response trend. The relative weights that the studied contributed to the meta-analyses were mostly evenly distributed across many studies. A key source of the heterogeneity may be due to the study in Singapore of Lee et al (Lee et al., 1994), the one study in which a dose-response trend was completely absent. The fact that this was one of the few studies not conducted in China may also be relevant. D. Factors influencing heterogeneity and meta-regression A factor that could contribute to the variability in the observed magnitude of associations is between-region differences in specific methods of salted fish preparation, and possibly with the type of fish consumed. This could potentially lead to differences in the risk associated with salted fish consumption but this is difficult to rigorously assess with so few studies, leaving an insufficient number of studies per region to analyze separately. The one study in which a positive dose-response relationship was absent was a study conducted in Singapore (Lee et al., 1994), one of only two studies included in the dose-response meta-analysis that took place outside of China. E. Important quality issues for interpretation of the evidence The dose-response meta-analyses of case-control studies to assess the association between salted fish intake at age 10 years and NPC yielded results indicating that NPC risk increases markedly with greater intake of salted fish. Clearly, the potential role that confounding factors may be contributing to this statistical association is a key consideration in interpreting this body of evidence. All nine of these studies included adjustments for at least age and sex, and five also further controlled for neighborhood of residence. Other factors considered included indicators of socioeconomic status (2 studies). Importantly, cigarette smoking, alcohol drinking, and dietary factors were not taken into consideration in any of these studies. The absence of information on EBV infection status is particularly notable. The limited extent to which potential confounding variables have been controlled for is thus an important issue affecting the quality of the overall evidence. Another important issue related to quality of the evidence is the remote recall of diet, usually by the mother of the study participant. While the accuracy of reporting may be questionable, the main issue is the degree to which accuracy of reporting may differ by case-control status to introduce a bias. The consistency of the findings across studies conducted by different investigators in different locations suggests either this is unlikely to explain the findings or that the information bias is ubiquitous across studies. The former explanation seems more likely. Fourteen of the case-control studies could be included in highest-versus-lowest categories comparison. The results of this data summary strongly reinforce the evidence suggesting that salted fish intake at 10 years of age increases the risk of NPC. Of the 14 studies, only one reported an odds ratio of less than unity, whereas five studies reported odds ratios between 1.40 and 1.99, three studies reported odds ratios between 2.0 and 4.0, and in 5 studies odds ratios of greater than 4.0 were observed. Two of the 16 case-control studies that reported information concerning the association between childhood consumption of salted fish and NPC did not present sufficient data to be included in any of the quantitative data summaries. In a case-control study of 205 NPC cases and 205 controls carried out in China, Zheng et al reported in the text that cases were “significantly” more likely to have the highest salted fish consumption at age 10 years, without reporting a p-value or measure of association (Zheng et al., 1993). In a study in Malaysia comprised of 100 NPC cases and 100 controls, the case-control difference in current salted fish consumption in

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children was reported to be statistically significantly different (Armstrong et al., 1983a). This comparison was adjusted for age, sex, area of residence, and ethnicity. In summary, the case-control evidence is clear and consistent in suggesting that salted fish intake in 10-year-old children is associated with increased NPC risk. The evidence to specifically pinpoint the observed risks to salted fish would be more convincing if potential confounding factors had been more completely accounted for.

Funnel Plot for Dose-Response Analysis: Salted fish intake at age 10, Case-control studies


logR


-.5

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.5

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Funnel Plot for Highest vs. Lowest Analysis: Salted fish intake at age 10, Case-control studies


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s.e. of: logR0 .5 1

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Salted fish: Childhood consumption (Ages 0-3) A3 Case-control studies (10) A total of 10 case-control studies reported on the association between salted fish intake at during 0-3 years of age and NPC. Five of these studies reported data in sufficient detail to be included in a dose-response meta-

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analysis. The results of the dose-response meta-analysis based on the number of times salted fish was consumed per week when 0-3 years old showed evidence of a strong trend of increasing NPC risk as salted fish intake increased (summary random effects RR 1.42; 95% CI 1.11-1.81 per time/week). B2 Size of effect The magnitude of the summary RR (summary random effects RR 1.42; 95% CI 1.11-1.81 per time/week) observed in the dose-response meta-analyses indicates a strong dose-response association between salted fish intake at ages 0-3 years and NPC. B3 Biological Gradient The dose-response analyses are compatible with a strong dose-response trend between salted fish consumption and NPC, with a summary random effect RR of 1.42(95% CI 1.11-1.81 per time/week). The results from all five of the studies that contributed evidence to the meta-analysis were in the direction of increased risk, with dose-response ORs ranging from 1.21 to 1.84 per time/week. Four studies had OR point estimates of 1.21 to 1.21, with one study of relatively high influence reporting an OR of 1.84.

Dose-Response Graph: Salted fish intake at ages 0-3, Case-control studies

B4 Internal Consistency/heterogeneity by dietary methodology

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In these studies, salted fish intake was measured using study specific FFQs or dietary history questionnaires. All of the studies were hospital-based for case ascertainment. B5 Summary Illustrations of effects (e.g., forest plots)

Forest Plot for Dose-Response Analysis: Salted fish intake at ages 0-3, Case-control studies

Odds Ratio, times/week

.05 1 4

Study

Effect size

(95% CI) % Weight






Overall 1.42 ( 1.11, 1.81) 100.0

Forest Plot for Highest vs. Lowest Analysis: Salted fish intake at ages 0-3, Case-control studies


.01 1 60

Study

Effect size

(95% CI)







NAS01608 (Hong Kong, Yu, 1986) 20.20 ( 6.79, 60.06)

NAS01812 (Hong Kong, Geser, 1978) 2.60 ( 1.26, 5.37)

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B6 Gene-nutrient interactions Does not apply. C Assessment of heterogeneity within and between study types Within the case-control dose-response meta-analysis, statistically significant heterogeneity was detected, with an I2 statistics of 66%. The presence of a dose-response trend was observed so consistently in all five studies that the heterogeneity present relates primarily to the magnitude of the dose-response gradient, not with respect to the presence or absence of a dose-response trend. D. Factors influencing heterogeneity and meta-regression The only study that exhibited any variation from the narrow range of dose-response associations observed was the steeper dose-response gradient observed in a study conducted in Guangzhou, China (Zheng et al., 1994a). However, another study from this same region also reported findings that were more in keeping with the findings of others (Yu et al., 1989), suggesting that the heterogeneity is not due to regional variation in preservation techniques. E. Important quality issues for interpretation of the evidence The dose-response meta-analyses of case-control studies to assess the association between salted fish intake at ages 0-3 years and NPC yielded results indicating that NPC risk increases markedly with greater intake of salted fish. Clearly, the potential role that confounding factors may be contributing to this statistical association is a key consideration in interpreting this body of evidence. All five of these studies included adjustments for at least age and sex, and three also further controlled for neighborhood of residence. Other factors considered included indicators of socioeconomic status (2 studies). Importantly, cigarette smoking, alcohol drinking, and dietary factors were not taken into consideration in any of these studies. The absence of information on EBV infection status is particularly notable. The limited extent to which potential confounding variables have been controlled for is thus an important issue affecting the quality of the overall evidence. Another important issue related to quality of the evidence is the remote recall of diet, usually by the mother of the study participant. While the accuracy of reporting may be questionable, the main issue is the degree to which accuracy of reporting may differ by case-control status to introduce a bias. The consistency of the findings across studies conducted by different investigators in different locations suggests either this is unlikely to explain the findings or that the information bias is ubiquitous across studies. The former explanation seems more likely. Eight of the case-control studies could be included in highest-versus-lowest categories comparison. The results of this data summary strongly reinforce the evidence suggesting that salted fish intake at 0-3 years of age increases the risk of NPC. Of the eight studies, only one reported an odds ratio of unity, one study reported an odds ratio of 1.20, another 1.30, with the remaining five studies reporting odds ratios of 2.0 or greater. Two of the ten case-control studies that reported information concerning the association between early childhood consumption (0-3 years of age) of salted fish and NPC did not present sufficient data to be included in any of the quantitative data summaries. In a case-control study of 205 NPC cases and 205 controls carried out in China, Zheng et al reported in the text that cases were “significantly” more likely to have the highest salted fish consumption at ages 0-3 years, without reporting a p-value or measure of association (Zheng et al., 1993). Jeannel and colleagues specifically examined consumption of salted anchovies during weaning in a case-control study of 80 NPC cases and 160 controls in Tunisia (Jeannel et al., 1990a). The reported odds ratio was 1.5 with a p-value of 0.5. The results were adjusted for age, sex, area of residence, and living condition score. Thus, the studies not included in the quantitative syntheses of the evidence also tend support the findings observed in the meta-analyses.

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In summary, the case-control evidence is clear and consistent in suggesting that salted fish intake in children ages 0 to 3 years is associated with increased NPC risk. The evidence to specifically pinpoint the observed risks to salted fish would be more convincing if potential confounding factors had been more completely accounted for.

Funnel Plot for Dose-Response Analysis: Salted fish intake at ages 0-3, Case-control studies


logR

s.e. of: logR0 .2 .4 .6

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Funnel Plot for Highest vs. Lowest Analysis: Salted fish intake at ages 0-3, Case-control studies


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s.e. of: logR0 .2 .4 .6

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3

Salted fish: Mother’s consumption during pregnancy or breastfeeding A3 Case-control studies (3) Three case-control studies reported on the relationship between NPC and mother’s consumption of salted fish during pregnancy or while breastfeeding. Two of these studies were carried out in China, and the other took place in Singapore among individuals of Chinese ethnicity. Both of the studies conducted in China were carried out by Yu and colleagues. In the first of these studies, comparing 128 NPC cases with 174 controls, Yu and

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colleagues observed that both consumption of salted fish during pregnancy and during nursing were associated with increased subsequent risk of NPC in the offspring (Yu et al., 1988). The odds ratios for these associations were consistent with a greater than three-fold increased risk with 95% confidence intervals that did not overlap unity after adjusting for age and sex. These results were corroborated in the second of the studies carried out in China, also by Yu and colleagues (Yu et al., 1989), in which the odds ratios for these associations were consistent with a greater than two-fold increased risk with 95% confidence intervals that did not overlap unity after adjusting for age, sex, and neighborhood. These results were based on a comparison of 306 NPC cases with 306 controls. In the study conducted in Singapore by Lee and colleagues, 49 NPC cases were compared to 96 controls, and the results were adjusted for age, sex, ethnicity, and education (Lee et al., 1994). Due to the smaller sample size, among other factors, the 95% confidence intervals were quite wide, but the point estimates of the odds ratios for maternal salted fish consumption during pregnancy (1.3) and during breastfeeding (2.0) were again in the direction of increased risk, although the associations were weaker than in the studies conducted in China.

The results of these three studies thus provide evidence that maternal salted fish consumption during pregnancy and breastfeeding is statistically associated with subsequent risk of NPC in offspring. Prominent among the many factors that have not been accounted for in these studies is whether this observed association is due this measured exposure simply because it is a marker of subsequent salted fish consumption by the index youth. 4.2.5.3.2 Salted plant food Total preserved vegetables: Adulthood consumption A3 Case-control studies (2) A total of 2 case-control studies reported results for salted vegetables and NPC. A study by Zheng et al reported a significant risk association for salted vegetables, but did not provide more details (Zheng et al., 1993). In a study of 100 cases and 300 matched controls conducted in China, no significant associations were reported for salted vegetables (Ning et al., 1990). Total preserved vegetables: Childhood/Infancy consumption A3 Case-control studies (1) One case-control study investigated salted vegetables during childhood and risk of NPC. Ning et al observed no significant associations for salted vegetables at age 10 (Ning et al., 1990). Salted Root Vegetables A3 Case-control studies (1) The association between preserved root vegetables and NPC was evaluated in a single case-control study. Salted root vegetables were reported to be significantly associated with NPC among 97 cases and 192 controls in China (unadjusted OR=2.2; 95% CL: 1.3-2.2) (Zou, 1999). Salted Cruciferous Vegetables: Adulthood consumption A3 Case-control studies (2) Both studies reporting results for salted cruciferous vegetables consumed during adulthood included Chinese men and women from Singapore or China. In the study by Lee et al, results for salted mustard greens (OR=3.1,

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95% CI: 1.4-6.5) were reported as significant (Lee et al., 1994). Yu et al reported no significant association for salted mustard greens (Yu et al., 1986). Salted Cruciferous Vegetables: Childhood consumption A3 Case-control studies (2) Two studies focused on salted cruciferous vegetables and any age group below age 10 years. Both studies (Lee et al., 1994, Yu et al., 1988) examining the risk of salted mustard greens at age 10 showed no association. Yu et al also assessed consumption at ages 1-2 and weaning. No association was observed at ages 1-2, but salted mustard greens consumed during weaning were reported to be in the risk direction (OR=5.4, 95% CI: 1.2-23.8) in an ever-versus-never analysis. Yu et al observed no significant associations for salted cabbage or salted radish at age 10 and NPC. Salted Green Leafy Vegetables: Adulthood consumption A3 Case-control studies (1) One case-control study evaluated the association between salted green leafy vegetables and NPC. The study of Chinese in Malaysia reported an unadjusted odds ratio of 3.33 (95% CI: 1.84-6.01) when comparing more than weekly intake of salted green leafy vegetables to monthly consumption (Armstrong et al., 1998b). Salted Green Leafy Vegetables: Childhood consumption A3 Case-control studies (1) One case-control study evaluated the association between salted green leafy vegetables consumed during childhood and NPC. The study of Chinese in Malaysia reported an unadjusted odds ratio of 0.84 (95% CI: 0.45-1.58) when comparing more than weekly intake of salted green leafy vegetables at age 10 to monthly consumption (Armstrong et al., 1998b). Salted Vegetables: Adulthood consumption A3 Case-control studies (2) Zou et al observed a significant risk association for salted non-starchy vegetables when consumed more than 9 times a month (OR=2.28, 95% CI: 1.40-3.73) in a study of 100 cases and 202 controls in China (Zou, 1999). The other study (Chen et al., 1997) reported no significant association between salted vegetables and NPC. Salted Vegetables: Childhood consumption A3 Case-control studies (2) Two studies reported on salted vegetables consumed during childhood; both reported significant protective associations for intake at age 10. In the first study to examine salted vegetables (Chen et al., 1997), 104 cases and 104 controls were matched by age, sex, and area of residence and a logistic regression odds ratio of 0.76 (95% CI: 0.58-0.99) was observed. The second study (Huang, 1997) reported similar results (OR=0.755, 95% CI: 0.58-1.0) for salted vegetables. Other Salted Vegetables: Adulthood consumption A3 Case-control studies (2) Salted vegetables consumed during adulthood was investigated in 2 case-control studies, both reported significant risk associations with NPC. Armstrong et al observed more than weekly consumption of salted root

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to be a risk factor for NPC (OR=2.19, 95% CI: 1.33-3.62) in study of Chinese in Malaysia (Armstrong et al., 1998b). After adjusting for age, sex, education level, and dialect group, salted Chinese tuber consumption was significantly associated with NPC (OR=2.4, 95% CI: 1.1-5.2) in a study of Chinese in Singapore (Lee et al., 1994). Other Salted Vegetables: Childhood consumption A3 Case-control studies (3) In three studies, associations in the direction of increased risk were observed relating salted vegetable intake during childhood and NPC (Armstrong et al., 1998b, Lee et al., 1994). Salted root intake at age 10 was in the risk direction, but not significant in 2 studies. The first study of Chinese in Malaysia included 282 cases and 282 controls (Armstrong, 1998) and observed an odds ratio f 1.75 (95% CI: 0.98-3.10) for more than weekly consumption compared to monthly consumption. The second study to examine salted root included 128 cases and 174 controls from China (Yu et al., 1988) and reported an age and sex adjusted odds ratio of 3.2 (95% CI: 0.6-17.6) for daily consumption compared to rare intake. In the same study by Yu et al, a significant association was observed for chung choi consumption during weaning using a maximally adjusted model (OR=0.518, p=0.042). Sze chuan chye, a salted Chinese tuber, was not found to be associated with NPC (OR=1.4, 95% CI: 0.4-4.5) in a study of Chinese in Singapore which included 145 cases and 340 controls (Lee et al., 1994). Salted olives: Adulthood consumption A3 Case-control studies (1) One case-control study evaluated the relationship between salted olives consumed during adulthood and NPC. An adjusted odds ratio of 1.6 (95% CI: 0.3-7.5) was reported for intake of salted black olives more than once a month compared to no intake among 200 cases and 406 controls of Chinese in Singapore (Lee et al., 1994). Salted olives: Childhood consumption A3 Case-control studies (2) Two studies investigated the relationship between consumption of salted olives at age 10 and NPC risk. The first study of Chinese in Singapore reported a significant inverse association between salted black olives eaten more than once a month and NPC (OR=0.3, 95% CI: 0.1-0.9) (Lee et al., 1994). The second study of 128 cases and 174 controls conducted in China reported a non-significant association between salted olive intake at age 10 and NPC when adjusting for age and sex (Yu et al., 1988). Salted soy: Adulthood consumption A3 Case-control studies (2) Two case-control studies examined risks of NPC associated with exposure to salted soy consumption during adulthood. Lee et al showed significant positive associations (OR=6.7, 95% CI: 1.2-36.6) when the highest exposure was compared to the lowest (Lee et al., 1994). The second study only indicated a significant association with NPC in the text without providing details (Zheng et al., 1993). Salted soy: Childhood consumption A3 Case-control studies (1)

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One case-control study examined risks of NPC associated with exposure to salted soy consumption during childhood. Lee et al showed no significant association (OR=1.1, 95% CI: 0.5-2.2) when the highest exposure was compared to the lowest (Lee et al., 1994). Other salted pulses/legumes A3 Case-control studies (1) Salted black beans were not associated with NPC when consumed during adulthood (OR=2.1, 95% CI: 0.8-5.4) or at age 10 (OR=1.0, 95% CI: 0.4-2.3) in a study of Chinese in Singapore (Lee et al., 1994). 4.2.6 Pickling Total pickled foods A3 Case-control studies (1) One study reported on consumption of pickled foods and NPC. In a matched case-control study in China, evidence of a risk association (OR=3.21, 95% CI: 1.71-5.71) was observed for frequent consumption of pickled foods (Huang, 2002). Pickled vegetables: Adulthood consumption A3 Case-control studies (2) A total of 2 case-control studies reported results for pickled vegetables and NPC. In a study of 100 cases and 300 matched controls conducted in China, no significant associations were reported for pickled vegetables (Ning et al., 1990). The second study included 100 cases and 100 controls in China and observed a significant regression slope of 0.015 for the intake of pickled vegetables after adjusting for environmental factors, gas range, pungent foods, and socio-economic status (Duan, 2000). Pickled vegetables: Childhood/Infancy consumption A3 Case-control studies (2) Two case-control studies investigated pickled vegetables during childhood and risk of NPC. A study by Jeannel et al reported an adjusted odds ratio of 2.2 for consumption of pickled vegetables during weaning, but no other details were offered (Jeannel et al., 1990a). Ning et al observed no significant associations for pickled vegetables at age 10 (Ning et al., 1990). Pickled Root Vegetables A3 Case-control studies (1) The association between pickled root vegetables and NPC was evaluated in a single case-control study. In a Chinese study, pickled root vegetables consumed at age 10 were inversely associated with NPC (OR=0.75, 95% CI: 0.57-0.99) (Huang, 1997). Pickled Cruciferous Vegetables: Adulthood consumption A3 Case-control studies (2) Both studies included Chinese men and women from Singapore or China. The first study by Chen et al observed no significant association between pickled Chinese cabbage and NPC (Chen et al., 1997). In the

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second study, both pickled leaf mustard (OR=6.11, p<0.01) and pickled radish (OR=1.75, 95% CI: 1.10-2.79) were observed to be significantly related to NPC (Ye, 1995). Pickled Cruciferous Vegetables: Childhood consumption A3 Case-control studies (2) Two studies focused on pickled cruciferous vegetables and NPC. Both studies assessed the association between pickled cabbages at age 10. Chen et al reported a protective odds ratio of 0.75 (95% CI: 0.57-0.99) for pickled cabbage consumption at age 10, whereas Yu et al observed no significant association (Chen et al., 1997, Yu et al., 1988). Other Pickled Vegetables: Adulthood consumption A3 Case-control studies (2) Pickled vegetables consumed during adulthood was investigated in 2 case-control studies, both reported significant risk associations with NPC. An ever-versus-never odds ratio of 3.3 (p=0.03) was observed for pickled vegetables with fungus after adjusting for age, sex, area of residence, and living condition score in a Tunisian study of 80 cases and 160 controls (Jeannel et al., 1990a). Zou et al reported a significant risk for pickles (OR=2.2, 95% CI: 1.3-3.6) when consumed 9 or more times month in a Chinese study (Zou, 1999). Other Pickled Vegetables: Childhood consumption A3 Case-control studies (1) In one study an association in the direction of increased risk was observed in relation to pickled vegetable intake during childhood and NPC. Jeannel et al reported a significant risk association for pickled vegetables with fungus consumed during weaning (OR=3.8, p=0.03) in a study of Tunisian cases and controls (Jeannel et al., 1990a). Pickled olives: Adulthood consumption A3 Case-control studies (1) One case-control study evaluated the relationship between pickled olives consumed during adulthood and NPC. The study of 80 cases and 160 controls in Tunisia reported a maximally adjusted odds ratio of 8.7 for consumption of pickled olives in the year preceding diagnosis (Jeannel et al., 1990a). Pickled spice intake A3 Case-control studies (2) Two case-control studies examined the risk of NPC and exposure to pickled spices. Laouamri et al observed significant positive associations from an Algerian study which evaluated pickled peppers (OR=2.85, 95% CI: 1.25-6.45) (Laouamri et al., 2001). The second study observed a protective association for pickled chili consumed during 3 meals (OR=0.3, p<0.01) in a study of Chinese in Malaysia (Armstrong, 1978). 4.2.7 Curing and smoking No results found. 4.2.7.1 Cured foods

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No results found. 4.2.7.1.1 Cured meats Cured meat: Adulthood consumption A3 Case-control studies (2) Two case control studies addressed the question of whether consumption of cured meats in adults was associated with an increased risk of NPC. Ward et al found no significant risk associated with consumption of cured meats adjusting for age, sex, and ethnicity when comparing Taiwanese subjects on a never/ever intake basis (Ward et al., 2000). Ning et al examined consumption of cured meats and found no significant association with these foods and NPC (Ning et al., 1990). Cured meat: Childhood consumption A3 Case-control studies (2) Two case control studies addressed risks of NPC from consumption of cured meat in childhood. The Ward et al study in Taiwanese examined the risks for children exposed according to cured meats at age 10 years and observed no significant association (Ward et al., 2000). The study by Ning et al examined exposures to cured meats at age 10 and indicated non-significant associations without any further details (Ning et al., 1990). 4.2.7.1.2 Smoked foods Smoked meat: Adulthood consumption A3 Case-control studies (4) Four case control studies addressed the question of whether consumption of smoked meats in adults was associated with an increased risk of NPC. Two of the studies found no significant association between consumption of smoked meat products and occurrence of NPC. Ward et al found no significant risk associated with consumption of either cured or smoked meats adjusted for age, sex, and ethnicity when comparing Taiwanese subjects on a never/ever intake basis (Ward et al., 2000). Ning et al examined consumption of smoked meats and found no significant association with these foods and NPC (Ning et al., 1990). Two studies reported significant associations between exposure to smoked meats and NPC. The Chelleng et al study of consumption of smoked meats in Indians reported an odds ratio of 10.8 based on a never/ever exposed classification and adjusted for multiple household environmental variables as well as tobacco and alcohol use (Chelleng et al., 2000). Zou et al reported an ever-versus-never odds ratio of 1.8 (95% CI: 1.09-2.97) for smoked processed meat in a Chinese study (Zou, 1999). Smoked meat: Childhood consumption A3 Case-control studies (2) Two case control studies addressed risks of NPC from consumption of smoked meat in childhood. Both studies included only Chinese and indicated no significant associations between consumption of smoked meats at various ages in childhood and the risk of NPC adjusting for age and sex. The Ward et al study in Taiwanese examined the risks for children exposed according to smoked meats at age 10 years, 3 years and at weaning (Ward et al., 2000). The odds ratios were all between 1.1 and 2.2 using an ever/never exposure range. The study by Ning et al examined exposures to smoked meats at age 10 and indicated non-significant associations for all measures without any further details (Ning et al., 1990).

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4.3 Processing Processed meat: Adulthood consumption A3 Case-control studies (5) Five case-control studies have examined the relationship of processed meats to the risk of NPC Three studies were done in Chinese in China or in Singapore, one in the Philippines (West et al., 1993) and one in the USA with unknown ethnicity of the subjects (Farrow et al., 1998). All of the studies had between 100 and 250 cases. Four of the studies reported no significant association of consumption of processed meat and the risk of NPC. The Farrow study in the USA found no association with all processed meats based on the NCI food frequency questionnaire and no trend after adjustment for age sex energy intake and alcohol and smoking. The Lee et al study using a study-specific food frequency questionnaire to identify exposure to Chinese sausage found no association or trend after adjustment for age and sex (Lee et al., 1994). The Yu et al study examined liver sausage intake for subjects at age 10 and three years before diagnosis using a food frequency questionnaire and found no association after adjustment for age, sex and salted fish intake but with no details regarding the analysis (Yu et al., 1986). The West et al study of processed meats in general determined from an unspecified assessment instrument found a very low odds ratio of 0.46 based on tertiles of exposure that was of borderline significance when adjusted for the usual variables plus environmental factors, fish intake and herbal medicines. Only the study of Zou et al reported an association (odds ratio 1.8) between smoked processed meats and NPC without any adjustments for potential confounding variables (Zou, 1999).

Forest Plot for Highest vs. Lowest Analysis: Processed Meat, Case-control studies


.05 1 3

Study

Effect size

(95% CI)

NAS00700 (Farrow, 1998) 1.54 ( 0.71, 3.33)

NAS01056 (Lee, 1994) 1.00 ( 0.33, 3.06)

NAS01153 (West, 1993) 0.46 ( 0.21, 1.03)

NAS06023 (Zou, 1999) 1.80 ( 1.09, 2.97)

Processed meat: Childhood consumption A3 Case-control studies (3) Three studies reporting results for processed meat during childhood examined types of sausage and observed no significant associations. The three studies were all done in China and used study-specific food frequency questionnaires to identify exposures. The number of cases in the studies ranged from 128 to 250. All studies adjusted at least for age and sex. All reported that the odds ratios were non-significant for any association but

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only the Lee et al study reported the actual odds ratio as 0.8 (Lee et al., 1994). Both the Lee et al and the Yu et al study reported the association between Chinese sausage and liver sausage respectively based on exposure at age 10 (Lee et al., 1994, Yu et al., 1988). The Yu et al study reported the association between liver sausage exposure at age 10 years and 3 years before diagnosis as reported under the adult consumption (Yu et al., 1986). Processed pork A3 Case-control studies (3) Three case-control studies, all implemented in China, reported on the association between processed pork consumption and NPC. The studies ranged in size from 128 cases/174 controls to 250 cases/250 controls, and all used study-specific food frequency questionnaires to measure the dietary exposure. None of the studies reported measures of association, but rather only whether the results were “statistically significant” or not. The one study to report a significant increased NPC risk was for the exposure of “salted pork” (Zheng et al., 1993). Consumption of salted pork or pork sausage at age 10 years or as an adult was reported to be not significantly associated with NPC risk in two other studies (Yu et al., 1986, Yu et al., 1988). 4.3.1 Refining Bread: Adulthood consumption A3 Case-control studies (3) Three case-control studies reported on the potential association between eating bread as an adult and risk of NPC. Two of these studies were carried out in China. In the first of the studies in China, Yu and colleagues observed that bread consumption during adulthood (Yu et al., 1989) was not significantly associated with NPC risk. These results were only reported in the text of the paper. In the second of the studies carried out in China, the households of NPC cases were significantly less likely to often eat bread compared to the households of the controls (OR 0.43; 95% CL 0.27, 0.70) (Geser et al., 1978). The third study investigated Chinese living in Malaysia. In this study, cases were significantly more likely than controls to consume bread for breakfast, but further details were not reported (Armstrong, 1978). Interpreting the results of these three studies, which were very inconsistent, is hindered by the lack of detailed information. The inconsistent overall results could be a consequence of the heterogeneity in the exposures and study design features, or to fluctuation around an overall null result. Bread: Childhood consumption A3 Case-control studies (3) Three case-control studies reported on childhood bread consumption in relation to NPC risk. Two of these studies were carried out by Yu and colleagues in China. For these, the exposure measured was bread consumption at ten years of age. In results that were adjusted for at least age and sex, Yu and colleagues observed that bread consumption at age 10 years (Yu et al., 1989, Yu et al., 1988) was not significantly associated with NPC risk, as reported in the text of these papers. In contrast to these studies, the other study on this topic was conducted in Algeria and the exposure investigated was chewing bread crust during teething. In this study, the odds of chewing the crust of bread when teething were identical in NPC cases and controls (Laouamri et al., 2001). Overall, this evidence is consistent in suggesting that bread consumption during childhood is not associated with NPC. Noodles A3 Case-control studies (1)

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A study of Chinese in Malaysia compared 60 NPC cases to 150 controls with respect to the extent that the families of study participants ate noodles during meals. In matched analyses, the overall matched odds ratio of 1.2 indicates that families of cases were slightly more likely than the families of controls to eat noodles with their meals (Armstrong, 1978). In analyses by ethnic group, a stronger, statistically significant association was observed in the combined Hokkien plus Teochiu group. Rice A3 Case-control studies (2) Two studies reported on the association between eating rice and risk of NPC. A study of Chinese in Malaysia reported on the following associations: family eats rice for breakfast, family eats plain rice during evening meals, and family eats rice porridge during evening meal (Armstrong, 1978). Patterns of familial rice consumption were described in the text with very little detail. This study compared 60 NPC cases to 150 controls. A study carried out in China compared 104 NPC cases with 104 controls. In results that were unadjusted, eating rice at age 10 was inversely associated with risk of NPC (OR 0.71; 95% CI 0.51-0.92) (Huang, 1997). A5 Ecological studies (1) One study examined the per capita consumption of rice as determined in a food survey in both sexes of Chinese living in Hong Kong. The age-adjusted rates of NPC were significantly positively correlated with consumption of rice in both males and females (Koo et al., 1997). 4.3.2 Hydrogenation A3 Case-control studies (1) One case-control study reported on the relationship between dietary intake of margarine and the occurrence of NPC. In the study of Chinese in Singapore, more frequent margarine consumption at age 10 was inversely associated with NPC risk (OR 0.6; 95% CI 0.3-1.1), after adjusting for age, sex, ethnicity, and education (Lee et al., 1994). 4.3.3 Fermenting Fermented soy/tofu: Adulthood consumption A3 Case-control studies (6) Six case-control studies examined risks of NPC associated with exposure to fermented soy/tofu consumption during adulthood; however, only 2 provided enough detail for meta-analysis. The exposures included in this section were homogeneous in that all consisted of tofu/soy products that were not fresh. The studies were comparable in quality and only differed by the useable detailed information provided. None of the studies adequately controlled for other food intake that would allow evaluation of fermentation versus non-preservation of the same foods. Of the 6 studies in adults, 1 showed significant positive associations (Yuan et al., 2000b) and 1 showed non-significant positive associations (Zou, 1999), when the highest exposure was compared to the lowest. The remaining studies only indicated significant (Yu et al., 1989) or non-significant (Ning et al., 1990, Ward et al., 2000, Yu et al., 1986, Yu et al., 1989) associations with NPC in the text without providing details. Fermented soy/tofu: Childhood consumption A3 Case-control studies (6)

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Six case-control studies examined risks of NPC associated with exposure to fermented soy/tofu consumption during childhood; however, only 3 provided enough detail for meta-analysis. Studies of childhood intake of fermented tofu/soy products in relation to NPC risk (Lee et al., 1994, Ning et al., 1990, Ward et al., 2000, Yu et al., 1988) indicated no significant increased risk for fermented soy/tofu products. In fact, analyses by (Ward et al., 2000) and (Ning et al., 1990) suggested odds ratios below one, but (Yu et al., 1988) suggested significantly increased risks from consumption of fermented soy bean products. Other fermented pulses/legumes A2 Cohort studies (1) One cohort study reported the association between fermented pulses and NPC (Lin, 1997). A significant association (RR=12.7, 95% CI: 2.2-72.3) was observed for intake 6 or more times a week compared to intake less than twice a week when adjusting for age, EBV status, family history of NPC, and nasopharyngitis in the cohort of 9775 Chinese men in Taiwan. A3 Case-control studies (2) This exposure consisted of fermented black bean paste and fermented beans. Yu et al reported a high risk for fermented black bean paste when consumed at ages 1-2 (OR=4.6, 95% CI: 1.8-11.4), but not when consumed at age 10 (OR=1.4, 95% CI: 0.6-3.1) in a study from China (Yu et al., 1988). When consumed more than 9 times a month, fermented beans were reported as a risk factor for NPC (OR=2.1, 95% CI: 1.3-3.4) in another study from China (Zou, 1999). Fermented fish A3 Case-control studies (2) Two case-control studies contributed evidence concerning intake of fermented fish and NPC. Intake of fermented fish sauce at different ages was evaluated in a Chinese study by Yu et al (Yu et al., 1989). Although no estimates of risk were provided, no significance was reported for highest-versus-lowest analyses or over trends at any age of intake. Likewise, Yu et al reported no significant association for the consumption of fermented fish paste at age 10 (Yu et al., 1988). Fermented seafood: Childhood consumption A3 Case-control studies (1) One study investigated the risks of NPC associated with eating of fermented seafood in childhood. Yu et al examined the risks associated with consumption fermented crab or shrimp pastes at age 10 and found no association even after adjustment for basic variables (Yu et al., 1988). Fermented eggs A3 Case-control studies (2) Two case-control studies examined the risk of NPC associated with the consumption of fermented eggs (Ning et al., 1990, Yu et al., 1988). Both studies included Chinese from China and used study-specific food frequency questionnaires to identify exposures. Neither study specified the odds ratios but simply reported no significant associations between the cancers and duck eggs at 10 years of age or 3 years prior to diagnosis. Soy sauce A3 Case-control studies (3)

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Three case-control studies have examined the association of NPC with consumption of soy sauce. The studies used food frequency questionnaires except for the study of Armstrong et al that used recall as an assessment tool. The Armstrong et al study also evaluated the characteristics of the family exposure rather than the individual (Armstrong, 1978). One study had two sets of controls (Shanmugaratnam et al., 1978). All studies were in Chinese and most reported several factors used in adjustment. All studies resulted in non-significant associations between soy sauce and NPC. Other fermented condiment intake: Adulthood consumption A3 Case-control studies (2) Two case-control studies evaluated other fermented condiments in relation to NPC. Both studies included Chinese men and women, one in China (Yuan et al., 2000b) and the other in Hong Kong (Geser et al., 1978). No significant associations were reported for the consumption of fish sauce or oyster sauce in either study. Other fermented condiment intake: Childhood consumption A3 Case-control studies (1) One case-control study from China evaluated fermented condiments consumed during childhood and NPC. Yu et al reported non-significant associations for various condiments, including soy sauce, fish sauce, and oyster sauce, consumed at age 10 (Yu et al., 1988). 4.3.4 Compositional manipulation No results found. 4.3.4.1 Fortification No results found. 4.3.4.2 Genetic modification No results found. 4.3.4.3 Other methods No results found. 4.3.5 Food additives No results found. 4.3.5.1 Flavours A3 Case-control studies (3) Three case-control studies were ascertained that investigated flavours in relation to NPC. All of these studies were conducted in China. In the study of Zheng and colleagues, NPC cases (n=88) were slightly and non-significantly less likely than controls (n=176) to have used monosodium glutamate during the past year (OR 0.7; p=0.3), after adjusting for age, sex, area of residence, and socioeconomic status (Zheng et al., 1994b). In a

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study of flavour essence, Geser and colleagues observed significant difference between those who did and did not use flavour essence (Geser et al., 1978). Duan and colleagues, in a study of 100 cases and 100 controls, reported that consumption of pungent foods was significantly and inversely associated with NPC risk (Duan, 2000). Despite the homogeneity of all the studies being conducted in China, the heterogeneity in the flavours investigated in these studies makes it difficult to draw strong inferences. 4.3.5.2 Sweeteners (non-caloric) No results found. 4.3.5.3 Colours No results found. 4.3.5.4 Preservatives No results found. 4.3.5.4.1 Nitrites and nitrates A3 Case-control studies (1) In a case-control study of 378 cases and 327 controls in China, Ward and colleagues assessed nitrate and nitrate intake using a dietary questionnaire (Ward et al., 2000). After adjusting for age, sex, ethnicity, and total calories, adult intake of nitrate from fresh and preserved vegetables was inversely associated with NPC risk (OR 0.5; 95% CL 0.3, 0.8). Intake of nitrite from soybean products during infancy or childhood was not significantly associated with NPC, after adjustments for age, sex, ethnicity, and vegetable intake. A5 Ecological studies (3) The ecologic evidence concerning the potential association between nitrites/nitrates in drinking water and NPC comes from a trio of reports from China and Taiwan. In an ecologic study conducted in Guangdong, pickles in the high-risk area of Sihui contained significantly higher concentrations of nitrites/nitrates than the low risk area of Wuhua (Huang, 1988). This association had not been observed in an earlier study by Huang and colleagues (Huang, 1982). However, Huang and colleagues published another report in which an association in the risk direction was present but the difference was not significant (Huang, 1983). 4.3.5.5 Solvents No results found. 4.3.5.6 Fat substitutes No results found. 4.3.5.7 Other food additives No results found. 4.3.6 Packaging

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No results found. 4.3.6.1 Vinyl chloride No results found. 4.3.6.2 Phthalates No results found. 4.4 Preparation No results found. 4.4.1 Fresh food Fresh animal foods Fresh meat: Adulthood consumption A3 Case-control studies (4) Four case-control studies examined this exposure in China using study-specific food frequency questionnaires except for the study of Armstrong et al which evaluated exposure with a dietary history questionnaire. The three studies that examined consumption of fresh organ meats at any time prior to diagnosis and consumption of fresh meat and or fresh liver three years prior to diagnosis indicated no significant associations with these foods and NPC but provided no details regarding the conduct of the analysis (Ning et al., 1990, Yu et al., 1989, Yuan et al., 2000b). The study of Armstrong et al showed increased significant associations between NPC and both consumption of fresh liver at age 10 and 5 years prior to diagnosis as well as consumption of other pork/beef organs 5 years prior to diagnosis (Armstrong et al., 1998b). Exposures compared weekly consumption versus less than monthly and trend analysis for the liver consumption was also positive. None of the analyses were adjusted for any confounding variables. Fresh meat: Childhood consumption A3 Case-control studies (4) Four case-control studies examined the risks of NPC associated with childhood consumption of fresh meats. All studies but Armstrong et al used study-specific food frequency questionnaires and all showed no significant associations. The exposures included fresh meat at ages 10 and 1-2 and during weaning and one study specified consumption of fresh liver intake at age 10. None of the studies provided details of the analysis and all adjusted only for age and sex and sometimes area of residence (Ning et al., 1990, Yu et al., 1989, Yu et al., 1988). Only the Armstrong et al study reported a significant positive association with consumption of fresh liver at age 10 or 5 years before diagnosis but not with consumption of other organ meat at age 10 based on a dietary questionnaire (Armstrong et al., 1998b). The comparison of frequency of intake compared to less than monthly yielded a highly significant positive trend but the odds ratio of 2 was not adjusted for any potential confounding variables. Fresh fish

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A3 Case-control studies (3) Three studies from China evaluated intake of fresh fish at varying ages in relation to NPC risk. None of the studies observed significant associations for any of the age groups analyzed. In the first study (Yu et al., 1989), no significant associations were observed among matched cases and controls for intake of fresh fish sauce during adulthood, at age 10, or at ages 1-2. A second study by Yu et al reported similar non-significant associations for fresh fish consumption at age 10, at ages 1-2 (p=0.23), and during weaning (p=0.09) (Yu et al., 1988). Likewise, the third study by Ning et al reported non-significant results for boiled fish consumption during adulthood and at age 10 (Ning et al., 1990). Fresh seafood A3 Case-control studies (3) Three case-control studies examined the association between fresh shellfish and the risk of NPC. All studies included only persons of Chinese background. Two studies were done in China and used study-specific food frequency questionnaires. These studies included 100 cases (Ning et al., 1990) and 935 cases (Yuan et al., 2000b). Both of these studies reported no significant association of the cancer with exposures to fresh seafood generally (Yuan et al., 2000b) and crab or fresh jellyfish consumed at age 10 and in the three years prior to diagnoses in separate analyses. No details were given regarding the analyses. A study by Armstrong et al was done in Malaysia and used a dietary history questionnaire or recall (Armstrong, 1978). The study found a protective effect associated with the family eating fresh prawns at the evening meal or any meal with a significant odds ratio of 0.7 with adjustment for age, sex, race, SES, residence and lifestyle factors. Fresh eggs A3 Case-control studies (3) Three studies examined the risks of NPC associated with consumption of fresh eggs at different ages in Chinese from China (two studies) and Malaysia (Armstrong, 1978). All studies used a study-specific food frequency questionnaire except for Armstrong 1978 who measured exposures through recall. All studies adjusted for the basic variables of age and sex for at least some of the analyses with the exception of Yuan et al. None of the studies showed an association with exposure to fresh eggs at any age (Yuan et al., 2000b) or at age 10 years, at 1-2 years (Yu et al., 1988), or at weaning (Yu et al) with the exception of the Armstrong et al study that indicated a significant negative association for consumption of eggs by the family at evening meals. However, the same study showed no association with family consumption of eggs at other meals. Fresh milk A3 Case-control studies (1) One case-control study in China reported findings on consumption of fresh milk in relation to NPC. The study in China (Yuan et al., 2000b) reported that the findings between NPC and drinking fresh milk were not statistically significant in the text, without presenting measures of association. Fresh plant food Fresh vegetables: Adulthood consumption A3 Case-control studies (2) A total of 2 case-control studies reported results for fresh vegetables and NPC. Both studies were conducted in China and matched cases and controls. Yuan et al reported a maximally adjusted odds ratio of 0.85 (95% CI:

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0.65-1.10) when comparing intake more than 2.4 times a day to intake less than 1.5 times per day (Yuan et al., 2000b). The second study only reported a non-significant association between consumption of fresh vegetables 3 years prior to diagnosis and NPC (Ning et al., 1990). A5 Ecological studies (1) One ecological study examined the risk of NPC related to consumption of fresh vegetables in Chinese residents in Hong Kong. The study used per capita consumption to identify exposures and indicated significant correlations between the consumption of fresh vegetables and NPC after adjusting for age (r2=-0.77, p=0.009 among men and r2=-0.75, p=0.013 among women) (Koo et al., 1997). Fresh vegetables: Childhood/Infancy consumption A3 Case-control studies (2) Two studies reported on consumption of fresh vegetables early in life. In a case-control study in China, evidence of a protective association (OR 0.3 to 0.6) was observed for eating fresh non-preserved vegetables at age 10, at age 3, and during weaning, and for mother’s consumption during breastfeeding (Ward et al., 2000). The results of another Chinese study of intake at age 10 observed no significant association between fresh vegetable consumption and NPC (Ning et al., 1990). Fresh green vegetables: Childhood consumption A3 Case-control studies (1) One case-control study investigated the association between childhood consumption of fresh green vegetables and NPC. The study from China reported results for fresh green vegetable consumption during multiple childhood stages (Yu et al., 1989). A protective, yet non-significant, association was observed for consumption during weaning (OR=0.6, 95% CI: 0.3-1.1). Non-significant results in the direction of risk were reported for intake during ages 1-2 (OR=1.7, 95% CI: 0.6-4.9) and at age 10 (OR=1.3, 95% CI: 0.3-5.1). Other fresh vegetables A3 Case-control studies (1) A study of Chinese in Malaysia evaluated intakes of vegetables at different meals and the risk of NPC (Armstrong, 1978). A significant odds ratio of less than one was reported for vegetables eaten at breakfast and for fresh vegetables eaten at evening meals among families of participants. Among cases and controls, an odds ratio of 0.9 was reported for vegetables eaten at three main daily meals when adjusted for age, sex, census district, household type, race and ethnicity, and socioeconomic status. Fresh Cabbage: Adulthood consumption A3 Case-control studies (1) One study conducted in China evaluated the relationship between fresh cabbage consumption and NPC. In a large study of 935 cases and 1032 controls, no association was reported for daily intake and NPC when compared to less than weekly intake (OR=0.97, 95% CI: 0.81-1.17) of fresh bok choi (Chinese white cabbage) (Yuan et al., 2000b). Fresh Green Leafy Vegetables: Adulthood consumption A3 Case-control studies (1)

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One study from China examined the association between adulthood consumption of fresh green leafy vegetables and NPC. Yuan et al reported a non-significant maximally adjusted odds ratio of 1.25 (95% CI: 0.73-2.14) for fresh dark green leafy vegetables (Yuan et al., 2000b). Fresh Green Leafy Vegetables: Childhood consumption A3 Case-control studies (1) One case-control study from China studied the association between fresh green leafy vegetables and NPC. The study of 128 cases and 174 controls reported non-significant associations for fresh green leafy vegetables when consumed during weaning (p-for-trend 0.86), between ages 1-2 (p-for-trend 0.92), and at age 10 (Yu et al., 1988). Fresh Tomatoes: Adulthood consumption A3 Case-control studies (1) One study evaluated the relationship between fresh tomato consumption during adulthood and NPC. No association was assessed for daily intake in a large Chinese study of 935 cases and 1032 controls when maximally adjusted (OR=0.92, p-for-trend=0.10) (Yuan et al., 2000b). Other Fresh Vegetables: Adulthood consumption A3 Case-control studies (1) One study examined fresh vegetables consumed during adulthood and NPC. The study included 935 cases and 1032 controls from China and used a food frequency questionnaire to assess intake (Yuan et al., 2000b). Daily intakes of fresh light green/orange leafy vegetables (OR=0.98, 95% CI: 0.63-1.50), fresh gourds (OR=0.89, 95% CI: 0.73-1.09), and fresh green peppers (OR=0.67, p=0.43) were not shown to be associated with NPC when compared to less than weekly intake and adjusted for various confounders. Total fresh fruits: Adulthood consumption A3 Case-control studies (4) The evidence for fresh fruits consumed during adulthood was not amenable to meta-analysis since only 3 case-control studies provided sufficient information to be included. A protective odds ratio was reported in 2 studies (Armstrong, 1978, Huang, 1997), although only 1 was statistically significant (Armstrong et al). Zheng et al and Ning et al reported non-significant results for the consumption of fresh fruit using a matched case-control design (Ning et al., 1990, Zheng et al., 1994a). Total fresh fruits: Childhood consumption A3 Case-control studies (3) In three studies, associations were examined relating fresh fruit intake during childhood and NPC. All studies included Chinese cases and controls from China. Zheng et al and Ning et al reported non-significant results for fresh fruit consumption at age 10 or at ages 0-3 (Ning et al., 1990, Zheng et al., 1994a). The third study examined fresh fruit consumed around 2 different decades and observed significant protective associations for both (OR=0.67, 95% CI: 0.49-0.90 around 1968 and OR=0.68, 95% CI: 0.52-0.89) (Cai, 1996). Fresh citrus fruit: Adulthood consumption A3 Case-control studies (1)

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Yuan et al compared daily intakes of fresh oranges and tangerines to less than weekly intakes and reported a maximally adjusted odds ratio of 0.06 (p-for-trend 0.0005) (Yuan et al., 2000b). Fresh pulses/legumes A3 Case-control studies (1) In a study by Ward et al, the associations between fresh soybean products consumed at various ages and NPC were evaluated among Chinese men and women in Taiwan (Ward et al., 2000). No significant association was reported for consumption during adulthood. At ages 10 and 3, fresh soybean consumption was reported as protective, but was only significant for age 10 (OR=0.4, 95% CI: 0.-1.0 and OR=0.7, 95% CI: .3-1.7, respectively). Neither consumption during weaning (OR=1.1, 95% CI: 0.5-1.2) or mother’s consumption during breastfeeding (OR=0.7, 95% CI: 0.3-1.6) was observed to be associated with NPC. Mixed vegetables A3 Case-control studies (1) Fresh green beans and peas were reported as significantly protective for NPC (OR=0.77, 95% CI: 0.62, 0.99) when maximally adjusted for in a Chinese study of 935 cases and 1032 controls (Yuan et al., 2000b). 4.4.1.1 Raw A3 Case-control studies (2) Two case-control studies conducted by Armstrong and colleagues among Chinese in Malaysia reported on the associations between consumption of raw foods and NPC. Statistically significant trends in the protective direction were observed with greater consumption of raw green vegetables (p-for-trend 0.026) (Armstrong et al., 1998b) and sliced raw chilli (cases ate less at evening meals) (Armstrong, 1978). 4.4.1.2 Juiced No results found. 4.4.2 Cooked food A3 Case-control studies (2) The two studies that provided evidence for cooked food were conducted in China and concerned cooking of salted fish (Ning et al., 1990, Zheng et al., 1994b). The first study assessed fried or steamed salted fish consumption from ages 2-10 and before age 2 and observed no significance (OR=1.4, p=0.2 and OR=1.4, p=0.3, respectively). The second study also reported no significant association between fried, grilled, or broiled salted fish at age 10 and NPC (OR=1.6, 95% CI: 0.8-3.2). 4.4.2.1 Steaming, boiling, poaching A3 Case-control studies (1) In a single case-control study in China, steamed salted fish consumed at age 10 was significantly associated an increased risk of NPC (OR 4.2; 95% CL 2.2, 8.3), whereas boiled fresh fish intake at age 10 years or adulthood was not significantly associated with NPC (Ning et al., 1990). The factors adjusted for in this study were age, sex, and area of residence.

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4.4.2.2 Stewing, casseroling A3 Case-control studies (1) A “stewing mixture” of peppers, spices, and other ingredients was evaluated in relation to NPC in a case-control study in Tunisia (Jeannel et al., 1990a). Intake of this stewing mixture was significantly associated with increased NPC risk both during weaning (OR 8.4; p<0.005) and adulthood (OR 4.4; p=0.04) when adjusted for age, sex, lifestyle factors, and area of residence. 4.4.2.3 Baking, roasting No results found. 4.4.2.4 Microwaving No results found. 4.4.2.5 Frying A3 Case-control studies (1) The association between consumption of fried food and NPC was reported to be not statistically significant for intake three years prior to diagnosis and at 10 years of age (Ning et al., 1990). These results were based on a study in China with 100 cases and 300 controls, and after adjustment for age, sex, and area of residence. 4.4.2.6 Grilling (broiling) and barbecuing A3 Case-control studies (1) The association between consumption of grilled food and NPC was reported to be not statistically significant for intake three years prior to diagnosis and at 10 years of age (Ning et al., 1990). These results were based on a study in China with 100 cases and 300 controls, and after adjustment for age, sex, and area of residence. 4.4.2.7 Heating, re-heating No results found. 5 Dietary constituents 5.1 Carbohydrate No results found. 5.1.1 Total carbohydrate No results found. 5.1.2 Non-starch polysaccharides/dietary fibre No results found.

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5.1.2.1 Cereal fibre No results found. 5.1.2.2 Vegetable fibre No results found. 5.1.2.3 Fruit fibre No results found. 5.1.3 Starch No results found. 5.1.3.1 Resistant starch No results found. 5.1.4 Sugars No results found. 5.2 Lipids No results found. 5.2.1 Total fat No results found. 5.2.2 Saturated fatty acids No results found. 5.2.3 Monounsaturated fatty acids No results found. 5.2.4 Polyunsaturated fatty acids No results found. 5.2.4.1 n-3 fatty acids

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No results found. 5.2.4.2 n-6 fatty acids No results found. 5.2.4.3 Conjugated linoleic acid No results found. 5.2.5 Trans fatty acids No results found. 5.2.6 Other dietary lipids, cholesterol, plant sterols and stanols. No results found. 5.3 Protein No results found. 5.3.1 Total protein A3 Case-control studies (1) The sole case-control study to examine the association between protein consumption and NPC took place in China, and was comprised of a comparison of 935 NPC cases with 1032 controls. The results showed that greater intake of “all protein containing preserved foods” was associated with increased risk and the presence of a statistically significant dose-response trend (p-value 0.001), after adjusting for an extensive list of variables that included age, sex, education, cigarette smoking, and history of chronic ear and nose conditions (Yuan et al., 2000b). 5.3.2 Plant protein No results found. 5.3.3 Animal protein No results found. 5.4 Alcohol No results found. 5.5 Vitamins No results found.

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5.5.1 Vitamin A A3 Case-control studies (1) The sole report of vitamin A in relation to NPC was a study of Chinese in Malaysia comprised of 87 NPC cases and 79 controls. In this study, the association between consumption of foods rich in vitamin A and NPC was reported to be “not statistically significant (Armstrong et al., 1983a). The analyses included adjustments for, among other factors, age, sex, and neighbourhood. 5.5.1.1 Retinol No results found. 5.5.1.2 Provitamin A carotenoids Beta-carotene A3 Case-control studies (2) Two case-control studies have assessed the association between β-carotene intake and NPC. One of these studies was carried out in the U.S. and the other in Singapore. In the U.S. study, which was made up of 129 NPC cases and 206 controls, compared to those with lowest intake, those with highest consumption of β-carotene were observed to have lower risk of NPC (OR 0.5; 95% CL 0.22, 1.02) (Farrow et al., 1998). Variables adjusted for in the data analyses included age, sex, energy intake, alcohol drinking and cigarette smoking. The study in Singapore was comprised of 64 cases and 102 controls, and a protective association was observed in the comparison of the highest-versus-lowest third of intake (OR 0.7, 95% CL 0.4, 1.2) (Lee et al., 1994). In this study, factors adjusted for were age, sex, ethnicity, and education. Considered in total, both studies observed associations in the protective direct and the magnitude of the comparisons of the highest-versus-lowest categories of consumption were similar in the two studies, but the test for trend was not statistically significant in either study. 5.5.2 Non-provitamin A carotenoids No results found. 5.5.3 Folates and associated compounds No results found. 5.5.4 Riboflavin No results found. 5.5.5 Thiamin (vitamin B1) No results found. 5.5.6 Niacin

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No results found. 5.5.7 Pyridoxine (vitamin B6) No results found. 5.5.8 Cobalamin (vitamin B12) No results found. 5.5.9 Vitamin C A3 Case-control studies (3) Three case-control studies have evaluated the potential link between vitamin C intake and NPC, one in the U.S., one among Chinese in Singapore, and another among Chinese in Malaysia. In the U.S. study, compared to those with lowest intake, those with highest consumption of vitamin C were observed to have non-significant lower risk of NPC (OR 0.5; 95% CL 0.2, 1.0) with a test-for-trend that was of borderline statistical significance (p=0.06) (Farrow et al., 1998). These results were adjusted for age, sex, smoking, alcohol drinking and energy intake. The results of the two studies that took place in Singapore and Malaysia were not presented in enough detail to permit meaningful comparisons, only noting in the text that the case-control differences were not statistically significant (Armstrong et al., 1983a, Lee et al., 1994). 5.5.10 Vitamin D (and calcium) A3 Case-control studies (1) In a study of 23 cases and 69 controls in China, hair concentrations of calcium were 21% lower in cases than controls, a difference that was not statistically significant (Li, 1996). The results were unadjusted. A4 Cross-sectional studies (1) Serum vitamin D concentrations were significantly lower in NPC cases compared to controls in a cross-sectional study of 380 persons in China, based on a percentage difference of 10% (Li, 1996). A5 Ecological studies (1) In an ecologic study in China, it was observed that drinking water concentrations of calcium were significantly associated with NPC (Farrow et al., 1998) when comparing high risk areas to low risk areas. Similarly, serum calcium levels were significantly associated with NPC. 5.5.11 Vitamin E A3 Case-control studies (1) The sole case-control study to evaluate the association between vitamin E intake and NPC took place in China. In a comparison of 64 NPC cases with 102 controls, vitamin E intake was inversely associated with NPC risk (p-for-trend 0.01) (Lee et al., 1994). These findings were adjusted for age, sex, education, and ethnic group. 5.5.12 Vitamin K No results found.

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5.5.13 Other minerals A3 Case-control studies (1) One study, carried out in the U.S., investigated the link between vitamin supplement use and NPC. In this study, there were 129 NPC cases and 206 controls. Compared to nonusers, multivitamin users and supplement users had approximately one-half the risk of NPC (OR 0.55-0.56; 95% CL 0.31, 1.01). The results were adjusted for age, sex, energy intake, alcohol drinking, and cigarette smoking (Deng, 1995). 5.6 Minerals No results found. 5.6.1 Sodium No results found. 5.6.2 Iron A3 Case-control studies (3) Three case-control studies, each using different measurement tools, have evaluated the potential association between measures of iron intake and NPC. Two of the studies took place in China, the other in Kenya. The results have been mixed. In China, Deng and colleagues assessed concentrations of iron in serum, drinking water, and rice (Robinson et al., 1968). The mean iron concentrations of all three measures were similar in cases and controls. Iron concentrations in maize leaf were studied in Kenya, with the case-control comparison showing the mean iron concentration was 8% higher in cases that controls, reported as not statistically significant (Man et al., 1996). Hair concentrations in iron were 64% higher in cases than controls (p-value <0.05) in a study in China (Man et al., 1996). 5.6.3 Calcium (and Vitamin D) A3 Case-control studies (1) In a study of 23 cases and 69 controls in China, hair concentrations of calcium were 21% lower in cases than controls, a difference that was not statistically significant (Li, 1996). The results were unadjusted. A4 Cross-sectional studies (1) Serum vitamin D concentrations were significantly lower in NPC cases compared to controls in a cross-sectional study of 380 persons in China, based on a percentage difference of 10% (Li, 1996). A5 Ecological studies (1) In an ecologic study in China, it was observed that drinking water concentrations of calcium were significantly associated with NPC (Lajtman et al., 1994) when comparing high risk areas to low risk areas. Similarly, serum calcium levels were significantly associated with NPC. 5.6.4 Selenium A3 Case-control studies (3) Three case-control studies have reported on the association between selenium and NPC. Two of these studies were implemented in China, and the other took place in Croatia. All of the studies relied on biomarkers to

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measure selenium, and all three compared the mean serum selenium concentrations in cases and controls, and the results were unadjusted. In a study of 37 cases and 47 controls in Croatia, NPC cases had serum selenium concentrations that were 11% lower than controls, a difference that was not statistically significant (Yang et al., 1990). In a study of 111 cases and 56 controls in China, serum selenium concentrations were 13% lower in cases than controls (p-value<0.05) (Deng, 1995). A 42% case-control difference (p-value<0.01) in serum selenium concentrations was observed in a smaller (44 cases, 42 controls) study in China (Deng, 1995). In this latter study, selenium concentration in drinking water and rice were also measured. These comparisons also showed notably large case-control differences, with the concentration of selenium in drinking water 45% lower in cases than controls (p-value <0.01) and in rice 31% lower in cases than controls (p-value <0.001) (Man et al., 1996). The evidence to date, albeit limited by the few small studies that have not accounted for potential confounding variables, is nevertheless consistent in suggesting a protective association between selenium exposure and NPC. 5.6.5 Iodine A3 Case-control studies (1) Mean hair concentrations of iodine were 85% higher in cases than controls in a study of 8 cases and 30 controls in China, a difference that was not statistically significant (Ling-Wei et al., 1988). The results were unadjusted. 5.6.6 Other minerals Chromium A3 Case-control studies (2) Two case-control studies, both carried out in China, examined the association between exposure to chromium and NPC risk. Both of these studies assess chromium concentrations in drinking water, and both reported unadjusted medians or means for NPC cases and controls. A case-control comparison of drinking water concentrations noted that the median drinking water concentration of chromium in cases (n=45) was identical to that of the controls (n=30) (Deng, 1995). Deng and colleagues studied 44 NPC cases and 42 controls. In their study, the chromium concentration in drinking water, and observed that the mean of cases was 50% higher than controls (p-value <0.01) (Robinson et al., 1968). Deng and colleagues also reported on two additional measures of chromium exposure, in rice and drinking water. Serum chromium concentrations were observed to be 68% higher in cases than controls (p-value <0.01), and an even larger case-control difference (95%, p-value <0.01) was noted in the chromium concentrations in rice. Thus, strong differences in the direction of increased risk were seen for every exposure metric in this latter study, but the drinking water result was not corroborated in the only other study identified to report on this topic. Copper A3 Case-control studies (4) A total of four case-control studies reported on the association between copper exposure and NPC. Three of these studies took place in China; the other was conducted in Kenya. Copper was measured differently in each study, as the specific exposures were copper measured in maize leaf, in drinking water, in hair, in serum, and in rice. In the study of copper concentrations in maize leaf, conducted in Kenya, the mean exposure of NPC cases was only 2% less than in controls, a difference that was not statistically significant (Ling-Wei et al., 1988). The following three studies were all performed in China. In the study of Ling-Wei et al, the mean drinking water concentrations of copper were 24% higher in NPC cases than controls (p-value 0.05) (Man et al., 1996). The

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study of Man et al in China the mean copper concentrations in hair samples were almost identical in NPC cases (mean 14.25) and controls (mean 14.29) (Deng, 1995). In the third study, three different measures of copper were investigated, concentrations in serum, rice, and drinking water. In this study (Robinson et al., 1968), the mean copper concentrations in drinking water were 37% higher in cases than controls (p-value <0.01) and 139% higher in rice (p-value <0.05). However, the mean copper concentrations in the serum of cases and controls were not consistent with the other exposure metrics, as NPC cases had 4% lower serum concentrations than controls. Large case-control differences were observed for selected exposures in selected studies, but overall the results did not display strong consistency across studies or internal consistency in studies that used multiple exposure metrics. Manganese A3 Case-control studies (3) A total of three case-control studies reported on the association between manganese exposure and NPC. Two of these studies were carried out in China, whereas the third occurred in Kenya. Manganese was measured differently in each study, as the specific exposures were manganese measured in maize leaf, in drinking water, and in hair. In the study of manganese concentrations in maize leaf, conducted in Kenya, the mean exposure of NPC cases was only 4% greater than in controls, a difference that was not statistically significant (Ling-Wei et al., 1988). The following two studies took place in China. In the study of Ling-Wei et al, the mean drinking water concentrations of manganese were 21% higher in NPC cases than controls (p-value 0.05) (Man et al., 1996). The study of Man et al in China the mean manganese concentrations in hair samples were 12% lower in NPC cases than controls (Robinson et al., 1968). In summary, the results for manganese are inconsistent, and it is difficult to discern the degree to which heterogeneity in exposure assessment, as well as differences in study characteristics, contributed to the inconsistencies. Zinc A3 Case-control studies (4) The association between zinc exposure and NPC was reported on in a total of four case-control studies. One of these studies was carried out in Kenya, with the other three taking place in China. Zinc was measured differently in each study, as the specific exposures were zinc measured in maize leaf, in drinking water, in hair, in serum, and in rice. In the study of zinc concentrations in maize leaf, conducted in Kenya, the mean exposure of NPC cases was identical to that in controls (Ling-Wei et al., 1988). The following three studies were all performed in China. In the study of Ling-Wei et al, the mean drinking water concentrations of zinc were 59% higher in NPC cases than controls (p-value 0.01) (Man et al., 1996). Man et al observed mean zinc concentrations in hair samples were 5% lower in NPC cases than in controls (Deng, 1995). These results were unadjusted. In the third Chinese study, three different measures of zinc were investigated, concentrations in serum, rice, and drinking water. In this study (Robinson et al., 1968), the mean zinc concentrations in drinking water were 23% lower in cases than controls (p-value <0.05), 20% lower in cases than controls in rice (p-value <0.01), and the mean zinc concentrations in the serum of cases was 10% lower than controls (p-value <0.05). These means were unadjusted. The study of Deng and colleagues thus displays internal consistency in study findings across exposure categories for zinc in the protective direction, but these findings are counterbalanced by the results of the other studies. Other minerals A3 Case-control studies (2)

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Other minerals that have been studied for possible associations with NPC include boron, aluminum, antimony, magnesium, potassium, strontium, sulfur, and vanadium. The study the reported the results for boron was conducted in Kenya and published over three decades ago. This was a study of boron concentrations in maize leaf from Kenyan farms, and the results showed the mean concentrations were nearly identical for NPC cases and controls (Man et al., 1996). All of the other exposures reported on in this category stem from the study of Man et al in China. In this study, hair samples were collected from 29 NPC patients seen at a single hospital in Hong Kong and “95 unselected healthy people.” All the results were unadjusted. Man et al case-control percentage differences in mean concentrations in hair samples that were -34% for strontium (p-value <0.05) and +208% for vanadium (p-value <0.05) (Cohen, 2000, Griffin, 2000, Young et al., 2003). The case-control comparisons for the other exposures were reported to be not statistically significant. 5.7 Phytochemicals No results found. 5.7.1 Allium compounds No results found. 5.7.2 Isothiocyanates No results found. 5.7.3 Glucosinolates and indoles No results found. 5.7.4 Polyphenols No results found. 5.7.5 Phytoestrogens eg genistein No results found. 5.7.6 Caffeine No results found. 5.7.7 Other No results found. 5.8 Other bioactive compounds No results found.

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6 Physical activity 6.1 Total physical activity (overall summary measures) No results found. 6.1.1 Type of activity No results found. 6.1.1.1 Occupational No results found. 6.1.1.2 Recreational No results found. 6.1.1.3 Household No results found. 6.1.1.4 Transportation No results found. 6.1.2 Frequency of physical activity No results found. 6.1.3 Intensity of physical activity No results found. 6.1.4 Duration of physical activity No results found. 6.2 Physical inactivity No results found. 6.3 Surrogate markers for physical activity e.g. occupation No results found.

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7 Energy balance 7.1 Energy intake No results found. 7.1.1 Energy density of diet No results found. 7.2 Energy expenditure No results found. 8 Anthropometry 8.1 Markers of body composition No results found. 8.1.1 BMI No results found. 8.1.2 Other weight adjusted for height measures No results found. 8.1.3 Weight No results found. 8.1.4 Skinfold measurements No results found. 8.1.5 Other (e.g. DEXA, bio- impedance, etc) No results found. 8.1.6 Change in body composition No results found.

8.2 Markers of distribution of fat

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No results found. 8.2.1 Waist circumference No results found. 8.2.2 Hips circumference No results found. 8.2.3 Waist to hip ratio No results found. 8.2.4 Skinfolds ratio No results found. 8.2.5 Other e.g. CT, ultrasound No results found.

8.3 Skeletal size No results found. 8.3.1 Height (and proxy measures) No results found. 8.3.2 Other (e.g. leg length) No results found. 8.4 Growth in fetal life, infancy or childhood No results found. 8.4.1 Birthweight, No results found. 8.4.2 Weight at one year No results found.

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F. Narrative review on mechanistic studies All considerations on mechanistic factors associated with the development of nasopharyngeal carcinoma (NPC) must take into account the role of the Epstein-Barr virus (EBV), which has long been associated with the development of NPC, reviewed in (Cohen, 2000, Griffin, 2000). The IARC has listed EBV as a group 1 carcinogen, which is an agent that is definitively carcinogenic to humans. This virus is present in the tumor cells of all undifferentiated NPC and the majority of the less common squamous NPC. Further support for the role of EBV infection in the etiology of NPC is the observation that infection is common in areas where NPC is endemic, suggesting that infection of nasopharyngeal cells with the EBV virus is a necessary factor in the development of NPC. However, EBV infects the majority of the adult population in both areas with high rates of NPC and those areas where NPC is uncommon (Griffin, 2000). In addition, following primary infection with EBV, individuals remain lifelong carrier of the virus, but few individuals even in endemic areas ultimately develop NPC(Cohen, 2000). Thus, exposure to EBV and even chronic EBV infection is not sufficient for transformation to malignancy. EBV infection is most highly associated with nasopharyngeal carcinoma and lymphoma (Griffin, 2000). In particular, the endemic nature of NPC, in contrast to the widespread distribution of EBV infection, suggests the influence of either genetic or environmental exposures as additional risk factors in the development of NPC. Interactions between environmental and genetic factors are also possible and have been shown, and will be discussed below in the context of dietary influences for the development of nasopharyngeal carcinoma. EBV does not usually replicate following infection, but instead forms a monoclonal episome after cellular infection (Young et al., 2003). This viral latency is characterized by the expression of a subset of virus latent genes, while most other viral genes are not expressed. Transformation is associated with activation of specific viral proteins and in many cases the lytic cycle of the virus. Any potential influence of dietary factors on EBV related carcinogenesis involving the reactivation of EBV must therefore occur temporally after primary Epstein-Barr virus infection. There is evidence that the age of infection with the Epstein-Barr virus occurs somewhat unevenly in different populations(Chan et al., 2003, Yadav et al., 1987). In underdeveloped regions, primary infection with EBV usually occurs during the first few years of life and is often asymptomatic. In many NPC endemic areas, such as Malaysia and Hong Kong, infection is nearly universal by early childhood(Young et al., 2003). In developed populations, primary infection is more frequently delayed until adolescence or adulthood, in many cases producing the characteristic clinical features of infectious mononucleosis (Chan et al., 2003). Even in symptomatic infection (infectious mononucleosis), an earlier age of infection is seen in China in comparison to Western countries(Young et al., 2003). However, this simple association of early infection with NPC is complicated by high rates of childhood infection in regions, such as Japan and Africa(Young et al., 2003), without coincident increases in NPC risk. In addition, regional differences in incidence of NPC, for example in regions of China, cannot be accounted for by differences in incidence or onset of EBV infection. Thus additional factors must modulate the risk of the development of nasopharyngeal carcinoma following EBV infection. In both lymphoma and nasopharyngeal carcinoma, transformation is associated with expression of specific oncogenic viral proteins(Yoshizaki, 2002). Latent membrane protein 1 (LMP-1) is the major transforming protein of EBV which has been shown to be essential for B-cell transformation in vitro. Transformation by LMP-1 involves multiple changes(Liu et al., 2004), including alteration in surface adhesion proteins, induction of anti-apoptotic proteins (including BCL-2), induce cytokine production and to inhibit DNA repair (Li et al., 2004). Each of these changes may contribute to the fully transformed phenotype, which is further supported by the inhibition of metastatic potential following siRNA inhibition of LMP-1 in a EBV + nasopharyngeal

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carcinoma cell line C666 (Bouvier et al., 1991, Shao et al., 1988). LMP-1 is expressed in the majority of NPC, but is not present in all tumors, suggesting that additional factors may accompany transformation to NPC in EBV infected cells. However, factors which induce the expression of latent virus and viral proteins may therefore contribute to the emergence of transformed cells. Of the dietary factors that might influence the development of NPC, consumption of Chinese-style salted fish has been shown to increase the risk of developing NPC in EBV exposed populations consistently in many studies. This was again confirmed as the strongest dietary risk factor for the development of NPC in the current report. In particular, the risk is highest when consumption occurs during early childhood. As mentioned above, even though exposure to salted fish may occur as early as the weaning period (< 2 years), this dietary exposure would likely follow the development of chronic EBV infection following initial infection, since infection is almost universal in young children in these areas.

The timing of these events (onset of exposure to salted fish and infection with EBV) has not been thoroughly examined in any of the studies included in this report, but the proximity of these two contributing factors is of interest. Although comprehensive studies have not explored the association between environmental factors and EBV infection, some published reports suggest that the development of NPC following EBV infection may potentially be influenced by dietary exposures in two ways: by directly influencing the expression of viral proteins and through inducing genetic and epigenetic changes associated with the progression to invasive NPC.

Evidence for the reactivation of EBV from latently infected cells by dietary agents is primarily derived from Burkitt’s lymphoma cell lines. Raji, an EBV positive Burkitt’s lymphoma, has been shown to induce latent viral promoters when treated with extracts of Cantonese salted dried fish in vitro (Bouvier et al., 1991). The components of these extracts have not been identified, nor the mechanism by which these foods activate viral promoters, but appear to be separate from the mutagen content (Goldman et al., 2003). While such studies provide an interesting empirical link between dietary agents and EBV reactivation, an important transforming event in NPC progression, the lack of such studies in NPC cell lines and the unknown components of processed foods contributing to this activation, suggest that the precise role dietary agents play in EBV reactivation remain unstudied.

More studies have examined the role of nitrosamines and nitrites in salted fish as essential agents for transformation of NPC precursor tissues. Evidence suggests that high intake of nitrate and nitrosamine from salted fish account for some of this increased risk of NPC development. Nitrosamines are known mutagens and animal carcinogens that induce gene mutation through the formation of DNA adducts which if not repaired may lead to point mutations. The N-nitrosamines are a large group of compounds with a common carcinogenic mechanism(Zou et al., 1992, Zou et al., 1994). Salted fish has been shown to contain N-dimethylnitrosamine, N-diethylnitrosamine, N-nitrosopyrrolidene and N-nitrosopiperidine(Zou et al., 1992, Zou et al., 1994). Levels of these compounds were highest in salted fish from areas with the highest NPC mortality, while lower in areas with lower NPC mortality (Goldman et al., 2003). Exposure of the nasopharynx to these agents may be particularly damaging in that the carcinogenic properties of nitrosamines are greatest following oral administration. In addition, the variation in nitrosamine content of salted fish may contribute to heterogeneity in assigning risk to salted fish consumption in different geographic locations.

Alkylating agents including nitrosamines produce DNA adducts, specifically 7-methylguanine and O6-methylguanine. The O6-methylguanine is mostly responsible for the mutagenicity and carcinogenicity of these alkylating agents (Lin et al., 1992, Sun et al., 1993). Unfortunately, the genes targeted for mutational alteration in NPC have to a large degree not been identified, which does not allow a definitive association of nitrosamine exposure to tumor suppressor or oncogene mutation. Among the commonly mutated genes in other types of tumors, no reports describe mutation of k-ras and studies of mutation of the retinoblastoma gene(Lo et al., 1995,

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Sun et al., 1995) and p16/ CDKN2a (Burgos, 2003, Chakrani et al., 1995, Effert et al., 1992, Lo et al., 1992, Lung et al., 1998, Nasrin et al., 1994, Spruck et al., 1992, Sun et al., 1992, Van Tornout et al., 1997, Xie et al., 1997)have all been negative. The most extensively studied gene in NPC for mutational alterations is p53, also the most commonly mutated gene in other malignancies. Ten published studies in the last 12 years have reported mutation of p53 ranging from 0-27% of NPC tumors studied (Lung et al., 1998), with the 27% result in a study of only 11 tumors(Van Tornout et al., 1997). Overall, 18 of 282 tumors have been found to contain p53 mutations (overall percentage 6%), suggesting that mutations in p53 are not common and do not provide a connection between nitrosamines and the progression of NPC. However, in at least one study (Esteller et al., 1999), all 4 of the mutations detected were GC>AT, of particular mechanistic importance for alkylating agents.

The O6-methylguanine leads to GC->AT transitions in cell-culture and animal models if not repaired by O6-methylguanine methyltransferase (MGMT), and as described above, this lesion is produced by alkylating agents. MGMT has been shown to be altered in NPC, although through epigenetic changes, rather than mutational inactivation. Hypermethyaltion of the promoter region of MGMT silences expression of this gene in many cancers (Kwong et al., 2002, Wong et al., 2003) which has been reported in 20-28% of nasopharyngeal cancer (Esteller et al., 2001, Wolf et al., 2001). Inactivation of MGMT has been shown to be associated with the type of p53 mutations described above in lung and colon cancer(Goldman et al., 2003), but due to the infrequent mutations in NPC has not been studied . As noted above, LMP-1 produced by EBV reactivation may also reduce DNA repair capacity, compounding the mutagenic effects of nitrosamine compounds.

Additional support for the importance of nitrosamines in the carcinogenic process of NPC is provided by studies examining the cytochrome p450 enzyme CYP2E1. N-nitrosodimethylamine undergoes enzymatic hydroxylation catalyzed mainly by CYP2E1, a step in the activation of carcinogenic adducts (He et al., 2002). CYP2E1 is expressed in the nasopharynx and in NPC tumors(Hayashi et al., 1991). Increased activity of this enzyme would then result in increased activation of pro-carcinogens. A genetic polymorphism in the 5'-flanking region of the human CYP2E1, the C2 allele, affects binding of trans-acting factor to the promoter(Hayashi et al., 1991), This sequence change affects transcriptional regulation, resulting in up to 10-fold differences in promoter activity of the CYP2E1 gene(Hildesheim et al., 1997a, Hildesheim et al., 1995, Kongruttanachok et al., 2001). Studies have demonstrated an increased risk of developing NPC in patients with this variant form(Armstrong et al., 1998a), (relative risks of 2-2.5, higher in non-smokers), consistent with the increased formation of carcinogenic nitrosamines from salted fish for those individuals. These studies suggest genetic modifiers of environmental exposure contribute to the risks inherent in consumption of salted fish. Such genetic variation may contribute to the heterogeneity in studies examining risk of NPC following salted fish consumption.

In other food categories, for example salted vegetables, fermented legumes, pickled foods and other preserved food ingredients, a consistent positive association of consumption with risk of NPC was observed. Most striking was the reversal of the otherwise protective effects for green leafy vegetables observed in most studies when salted green leafy vegetables were examined(Jeannel et al., 1990b). A similar effect was seen for pickled olives in comparison to other fruits(Armstrong et al., 1998a). Each of these analyses suggests that food preparation, rather than food substance, is important for this increased risk of consumption. Few, if any, studies have determined the components or substances that might account for this increased risk from food preservation itself, as this risk was not previously recognized. Future studies may determine whether nitrosamines are key components of the fermentation process in these foods as has been shown for salted fish.

Protective dietary effects include vegetables, which may mediate effects through multiple components, including beta-carotene, alpha-tocopherol, retinoids, sulphoraphane and folate. This report found the most clear protective effect from leafy vegetables which was not seen when salted green leafy vegetables were examined(Giovannucci, 2002). For leafy vegetables, some of the protective effect is often attributed to folate

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intake, which is also seen in many other fruits and vegetables. Folate deficiency may increase the risk of NPC by inducing an imbalance in DNA precursors, leading to altered DNA synthesis and repair which has been the most widely studied in colon cancer(Allday et al., 1990, Ernberg et al., 1989, Hu et al., 1991). This effect is mediated through interaction with methionine levels, ultimately changing levels of S-adenosylmethionine and methylene-tetrahydrofolate, leading to affects on DNA synthesis and the epigenetic modification of DNA methylation. Thus folate deficiency could lead to mutational events and affect DNA methylation patterns that have been observed in NPC. Mechanisms involving changes in methylation relevant for tumor genesis include reactivation of latent EBV virus associated with loss of methylation of viral promoters (Chow et al., 2004, Hui et al., 2003, Kao et al., 2002, Kwong et al., 2002, Lo et al., 1996, Lo et al., 2002a, Lo et al., 2002b, Qiu et al., 2004, Sze Wong et al., 2002, Wong et al., 2002) and increased methylation of important tumor suppressor genes(Yokoyama et al., 2003).

Based on the present analyses, ethanol intake was not associated with increased risk of NPC, but an association of alcohol intake with increased risk for other upper aerodigestive tumors makes this association plausible. Interactions between alcohol drinking and EBV have not been directly explored. A recent review summarizes the increased risk associated with esophageal and head and neck cancer, as well as possible mechanisms behind this association(Poschl et al., 2004). This positive influence may be attributed to the formation of acetaldehyde, an oxidized product of ethanol. Acetaldehyde is carcinogenic and mutagenic, binding to DNA and protein(Poschl et al., 2004). Ethanol is eliminated from the body by its oxidation, first to acetaldehyde and then to acetate. These reactions are sequentially catalyzed by alcohol dehydrogenase and aldehyde dehydrogenase. Most of the acetaldehyde generated during alcohol metabolism in vivo is promptly eliminated by aldehyde dehydrogenase-2 (ALDH2), the low-Km mitochondrial ALDH. However, a mutant form of ALDH2, ALDH2*2 allele (Glu487Lys) encodes a catalytically inactive protein. The inactive form of ALDH2 with the mutant ALDH2*2 allele is common in people of Japanese descent. The distribution of the ALDH2*2 allele varies by race, being prevalent in East Asians, but not in Caucasians or Africans. When this enzyme is inactive, the body fails to metabolize acetaldehyde rapidly, leading to excessive accumulation of acetaldehyde. Thus, genetic predisposition may amplify the toxic and mutagenic effects of alcohol consumption. While this effect has been primarily attributed to esophageal and head and neck cancer, it is possible that similar effects may occur in other upper aerodigestive tumors including NPC, as exposure to these tissues would be similar.

Chronic alcohol consumption also induces cytochrome P450 enzyme (CP2E1) activity in mucosal cells (Giovannucci, 2002). As discussed above, the resulting increased activation of various dietary and environmental carcinogens would increase the mutagenic effects of dietary nitrosamines. In addition, alcohol intake has been shown to affect folate levels through inhibition of folate absorbance and through increased excretion of folate by the kidneys. Resulting folate deficiency may contribute to the accumulation of additional genetic and epigenetic alterations, as discussed above. All of these effects may contribute to the increased risk of NPC potentially seen in patients with consumption of alcohol. 6. Discussion Even for the exposures for which a sufficient quantity of evidence was available to assess for the presence of a dose-response trend, the meta-analyses of dose-response data was entirely limited to frequency of consumption. Ideally, one would like additional information on serving size and duration of use to integrate a more complete dose metric into the assessment of the evidence. Unfortunately, this more comprehensive dose assessment approach that measured amounts consumed or the total duration of consumption was available for only a few studies. If one had to choose a single measure of dose for the exposures most relevant to this SLR, such as preserved foods, the frequency of consumption may in fact be the most relevant measure.

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Although some studies have looked at diet in periods three to five years prior to the onset of cancer, most have not reviewed intake to time of expected latency of cancer. In studies that measured frequency of food intake during childhood years, the implicit assumption in the interpretation of most investigators seems to be that early age at intake is a susceptibility factor. An alternative explanation is that this is a proxy measure of duration of consumption, as food habits cultivated in childhood may track into adulthood. For some exposures, there was an insufficient quantity of data to perform a meta-analysis based on dose-response data. To expand the number of exposures for meta-analysis, we performed a meta-analysis for the exposures that had enough (n=5 case-control) studies for a combined analysis using the highest exposure categories as recommended by WCRF. The entire body of evidence on diet, nutrition, and NPC would be strengthened if it were possible to generate additional evidence from prospective studies. For practical considerations relating to the relatively rare occurrence of this cancer there are many advantages to case-control studies, so it seems unlikely this situation will markedly change in the near term. A large proportion of the studies related to the risk of NPC related to foods took place in China where risks are high. Even so, the number of cases in many of studies was still relatively small. A unique aspect of this SLR is the search of the literature published in Chinese. Bias could potentially be introduced if the results of the peer-reviewed Chinese literature differed from the non-Chinese literature, and this was due to methodological differences that affected study quality. Our impression was that this was not a critical issue, but in general in this SLR it was not uncommon for the articles to omit details that would be expected in the highest quality epidemiologic studies. For example, few studies have discussed the problems of recall of dietary data for case-control studies especially when childhood consumption is a point of query. Most of the studies the contributed data to the meta-analyses adjusted for at least age, sex, and area of residence. Some of the studies also included OR estimates that were adjusted for additional factors such as personal history of nasal disease, family history of NPC, cigarette smoking, alcohol intake, and exposure to environmental factors. Few studies actually examined the data to determine whether these were actually confounding variables in, for example, Chinese populations. Infection or reactivation with EBV could be a key issue, yet none of the studies accounted for EBV. A relatively small proportion of studies accounted for other dietary factors when reporting the results for a specific dietary factor. We have not yet had the opportunity to assess the quantitative impact such adjustments may have had on the observed associations when they were performed, but our anecdotal impression is that the observed associations tended to be strengthened when other dietary factors were accounted for in the analyses. Food-specific results tended to be presented in these papers. For a relatively homogeneous exposure, such as salted fish, this was not a problem. The reliance on the food-specific approach was more problematic for foods that were classified into broader food classes, such as citrus fruits or cruciferous vegetables. Rarely did papers report results for the summed results across broader food classes such as these. For example, for exposures such as fruits and vegetables, results for preserved and non-preserved foods within a specific WCRF exposure category were reported separately and only one could contribute to the meta-analysis. In this situation, foods were separated within the broad exposure categories and only meta-analysed when sufficient data was available within the subgroups. This limited possibilities for some exposures to be included in meta-analyses by reducing the total number of studies within a given subgroup. Similar separation methods were implemented for adult versus childhood timing of exposures. In this SLR we took care to note the findings reported in the text even without detailed results. Particularly for the results for which meta-analyses were possible, the reader is encouraged to pay close attention to the results

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of these studies when assessing the entire body of evidence, as these results tended to be reported simply as “non-significant.” The results of the meta-analysis hinted that the association between salted fish and NPC may be stronger in 0-3 year olds than among older children and adults. Coupled with the fact that the age distribution of the NPC cases in the Chinese studies tended to be young, the possibility that early infection with EBV combined with early exposure to salted fish may accelerate NPC carcinogenesis is of interest. An examination of the specific studies, although limited, may provide some specific data that could determine time to tumor. Mechanistic studies that evaluate the interaction between dietary exposures and EBV in NPC cell lines would provide evidence to help guide interpretation concerning biologic plausibility of the epidemiologic evidence.

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NPC: Summary Tables: 22 May, 2006

Reasons for inclusion in summary 1) exposure convincing, probable or possible in 1997 report, 2) at least 2 cohort or at least 5 case-control studies, 3) robust and reproducible human or animal experimental studies 4) Other – please state reason

Table of numbers of studies found and included in meta-analyses by study design Exposure Cohort studies Case-control studies Total

n Number Included in meta-analysis

Summary OR and 95% CI (Random)

Total n

Number Included in meta-analysis


Additional issues/ or reasons meta-analysis not appropriate

Included in summary (indicate reason)

1.2 Socio-economically defined diets

0 0 N/A 1 0 N/A <5 case-controls

1.3 Culturally defined diets


1.5 Other dietary patterns


1.6.2 Breast-feeding, child


1.7 Other dietary pattern issues


2.1.1 Cereal (grains) Adulthood consumption 0 0 N/A 1 0 N/A <5 case-controls Childhood consumption 0 0 N/A 2 0 N/A <5 case-controls 2.1.1.1 Wholegrain cereals


2.1.1.2 Refined cereals and cereal products Bread:

Adulthood consumption 0 0 N/A 3 0 N/A <5 case-controls Childhood consumption 0 0 N/A 3 0 N/A <5 case-controls

Noodles 0 0 N/A 1 0 N/A <5 case-controls Rice 0 0 N/A 2 0 N/A <5 case-controls;

1 ecological study

2.1.2 Starchy roots, tubers and plantains


2.2 Fruit and (non-starchy vegetables)


2.2.1 Non-starchy vegetables Total vegetables:

Adulthood consumption 0 0 N/A 5 0 N/A 2 ecological studies Case-control: 4 Highest vs. Lowest

Childhood consumption 0 0 N/A 3 0 N/A <5 case-controls Green vegetables:

Adulthood consumption 0 0 N/A 4 0 N/A <5 case-controls



Exposure Cohort studies Case-control studies Total



Total n





Childhood consumption 0 0 N/A 3 0 N/A <5 case-controls Preserved vegetables:

Adulthood consumption 0 0 N/A 7 0 N/A Only 2 studies could be included in meta-analysis

2

Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls Other vegetables 0 0 N/A 2 0 N/A <5 case-controls

2.2.1.1 Non-starchy root vegetables and tubers Total root vegetables 0 0 N/A 1 0 N/A <5 case-controls

Carrots: Adulthood consumption 0 0 N/A 2 0 N/A <5 case-controls Childhood consumption 0 0 N/A 6 0 N/A Case-control:

4 Highest vs. Lowest Preserved root veg 0 0 N/A 2 0 N/A <5 case-controls

2.2.1.2 Cruciferous vegetables Cabbage 0 0 N/A 3 0 N/A <5 case-controls

Other non-preserved: Adulthood consumption 0 0 N/A 5 0 N/A Heterogeneous exposures

(kale, rutabagas, turnip root, mustard, cauliflower)

2

Childhood consumption 0 0 N/A 6 0 N/A Heterogeneous exposures (kale, rutabagas, turnip root, mustard, cauliflower)

2

Preserved vegetables: Adulthood consumption 0 0 N/A 5 0 N/A Heterogeneous exposures

(pickled radish, sour cabbage, salted mustard)

2

Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls 2.2.1.3 Allium vegetables


2.2.1.4 Green leafy vegetables Total green leafy:

Adulthood consumption 0 0 N/A 4 0 N/A <5 case-controls Childhood consumption 0 0 N/A 2 0 N/A <5 case-controls

Water spinach 0 0 N/A 1 0 N/A <5 case-controls Total green leafy:






Total n





Adulthood consumption 0 0 N/A 3 0 N/A <5 case-controls Childhood consumption 0 0 N/A 2 0 N/A <5 case-controls 2.2.1.5 Other non-starchy vegetables

Tomatoes: Adulthood consumption 0 0 N/A 5 0 N/A Case-control:

4 Highest vs. Lowest Childhood consumption 0 0 N/A 3 0 N/A <5 case-controls

Other non-preserved: Adulthood consumption 0 0 N/A 3 0 N/A <5 case-controls Childhood consumption 0 0 N/A 2 0 N/A <5 case-controls

Total preserved: Adulthood consumption 0 0 N/A 5 0 N/A Case-control:


Other preserved: Adulthood consumption 0 0 N/A 5 0 N/A Heterogeneous exposures

(dried tomato, salted root, plum vegetables)

2

Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls 2.2.1.6 Raw vegetables 0 0 N/A 2 0 N/A <5 case-controls 2.2.2 Fruits (general)

Total non-preserved: Adulthood consumption 0 0 N/A 6 0 N/A Only 3 studies could be

included in meta-analysis 2

Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls Preserved fruits 0 0 N/A 1 0 N/A <5 case-controls

2.2.2.1 Citrus fruits Total citrus fruits:

Adulthood consumption 0 0 N/A 5 0 N/A Case-control: 5 Highest vs. Lowest

Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls Preserved citrus fruits 0 0 N/A 1 0 N/A <5 case-controls

2.2.2.2 Other fruits Non-preserved fruits:

Adulthood consumption 0 0 N/A 2 0 N/A <5 case-controls






Total n





Childhood consumption 0 0 N/A 5 0 N/A Heterogeneous exposures (grapes, bananas, peaches, apples, watermelons)

2

Preserved plums: Adulthood consumption 0 0 N/A 4 0 N/A <5 case-controls Childhood consumption 0 0 N/A 5 0 N/A Only 2 studies could be


Preserved olives: Adulthood consumption 0 0 N/A 3 0 N/A <5 case-controls Childhood consumption 0 0 N/A 2 0 N/A <5 case-controls Other preserved fruits:

Adulthood consumption 0 0 N/A 3 0 N/A <5 case-controls Childhood consumption 0 0 N/A 2 0 N/A <5 case-controls 2.3 Pulses(legumes)

Non-preserved pulses 1 0 N/A 2 0 N/A <2 cohort; <5 case-controls Preserved soy/tofu:

Adulthood consumption 0 0 N/A 8 0 N/A Only 3 studies could be included in meta-analysis

2

Childhood consumption 0 0 N/A 6 0 N/A Only 3 studies could be included in meta-analysis

2

Other preserved pulses 1 0 N/A 3 0 N/A <5 case-controls 2.4 Nuts and seeds Adulthood consumption 0 0 N/A 3 0 N/A <5 case-controls Childhood consumption 0 0 N/A 2 0 N/A <5 case-controls 2.5.1 Meat

Preserved meat: Adulthood consumption 0 0 N/A 7 0 N/A Only 3 studies could be


Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls 2.5.1.1 Fresh meat Adulthood consumption 0 0 N/A 4 0 N/A <5 case-controls Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls 2.5.1.2 Processed meat Adulthood consumption 0 0 N/A 5 0 N/A Case-control:

4 Highest vs. Lowest






Total n





Childhood consumption 0 0 N/A 3 0 N/A <5 case-controls 2.5.1.3.1 Beef 0 0 N/A 2 0 N/A <5 case-controls;

1 ecological study

2.5.1.3.2 Pork 0 0 N/A 3 0 N/A <5 case-controls; 1 ecological study

2.5.1.3.4 Organ meats Non-processed organs: Adulthood consumption 0 0 N/A 4 0 N/A <5 case-controls Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls Processed organ meats 0 0 N/A 2 0 N/A <5 case-controls 2.5.1.4 Poultry 0 0 N/A 2 0 N/A <5 case-controls;

1 ecological study

2.5.2 Fish: non-preserved

0 0 N/A 3 0 N/A <5 case-controls; 1 ecological study

2.5.2.1 Salted fish Adulthood consumption 1 0 N/A 21 9 1.28

(1.13-1.44), times/week

Case-control: 9 Dose-Response; 17 Highest vs. Lowest

Consumption, age 10 1 0 N/A 16 9 1.35 (1.14-1.60), times/week


Consumption, ages 0-3 0 0 N/A 10 5 1.42 (1.11-1.81), times/week


Mother’s consumption 0 0 N/A 3 0 N/A <5 case-controls 2.5.2.2 Other preserved fish

1 0 N/A 5 0 N/A Heterogeneous exposures (dried, fermented, pastes)

2

2.5.3 Shellfish and other seafood Non-preserved seafood 0 0 N/A 4 0 N/A <5 case-controls

Preserved seafood: Adulthood consumption 0 0 N/A 5 0 N/A Only 3 studies could be


Childhood consumption 0 0 N/A 5 0 N/A Only 2 studies could be included in meta-analysis

2

2.5.4 Eggs






Total n





Non-preserved eggs 0 0 N/A 4 0 N/A <5 case-controls; 1 ecological study

Salted eggs: Adulthood consumption 0 0 N/A 5 0 N/A Only 3 studies could be


Childhood consumption 0 0 N/A 4 0 N/A <5 case-controls Other preserved eggs 0 0 N/A 5 0 N/A Heterogeneous exposures

(dried, fermented, tinned) 2

2.6 Fats, oils and sugars


2.6.1 Animal fats 0 0 N/A 3 0 N/A <5 case-controls 2.6.2 Plant oils 0 0 N/A 4 0 N/A <5 case-controls 2.6.4 Sugars 0 0 N/A 1 0 N/A <5 case-controls 2.7 Milk and dairy products


2.8 Herbs, spices and condiments Childhood consumption 0 0 N/A 3 0 N/A <5 case-controls

Herbal intake 0 0 N/A 6 0 N/A Case-control: 4 Highest vs. Lowest

Non-preserved spices 0 0 N/A 3 0 N/A <5 case-controls Preserved spices 0 0 N/A 4 0 N/A <5 case-controls

Soy sauce 0 0 N/A 3 0 N/A <5 case-controls Other fermented sauce 0 0 N/A 2 0 N/A <5 case-controls

2.9 Composite foods 0 0 N/A 14 0 N/A Heterogeneous exposures (soups, stews, porridges)

3.1 Total fluid intake 0 0 N/A 1 0 N/A <5 case-controls 3.2 Water 0 0 N/A 2 0 N/A <5 case-controls 3.3 Milk (as beverage) 0 0 N/A 4 0 N/A <5 case-controls 3.5 Fruit juices 0 0 N/A 1 0 N/A <5 case-controls 3.6 Hot drinks 0 0 N/A 1 0 N/A <5 case-controls 3.6.1 Coffee 0 0 N/A 3 0 N/A <5 case-controls 3.6.2 Tea Adulthood consumption 0 0 N/A 7 0 N/A Case-control:







Total n





3.6.2.2 Green tea 0 0 N/A 1 0 N/A <5 case-controls 3.7 Alcoholic drinks 0 0 N/A 1 0 N/A <5 case-controls 3.7.1 Total alcohol 1 0 N/A 18 8 1.01

(1.00-1.03), drinks/wk

<2 cohorts Case-control: 8 Dose-Response; 10 Highest vs. Lowest

3.7.1.1 Beer 0 0 N/A 3 0 N/A <5 case-controls 3.7.1.2 Wines 0 0 N/A 4 0 N/A <5 case-controls 3.7.1.3 Spirits 0 0 N/A 3 0 N/A <5 case-controls;

1 ecological study

3.7.1.4 Other alcoholic drinks


4.1.2 Chemical contaminants


4.1.2.7.1 Cadmium 0 0 N/A 2 0 N/A <5 case-controls 4.1.2.7.2 Arsenic 0 0 N/A 1 0 N/A <5 case-controls;

3 ecological studies

4.1.2.7.3 Other heavy metals Lead 0 0 N/A 3 0 N/A <5 case-controls

Mercury 0 0 N/A 1 0 N/A <5 case-controls Molybdenum 0 0 N/A 2 0 N/A <5 case-controls

Nickel 0 0 N/A 2 0 N/A <5 case-controls 4.1.2.9 Other contaminants

0 0 N/A 1 0 N/A <5 case-controls; 1 ecological studies

4.2 Preservation Preserved animal food 1 0 N/A 5 0 N/A Heterogeneous exposures

(meat, fish, eggs, dairy) 2

Preserved plant food 0 0 N/A 12 0 N/A Heterogeneous exposures (tomatoes, plums, roots)

2

4.2.1 Drying Dried animal food 0 0 N/A 5 0 N/A Heterogeneous exposures

(fish, shrimp, oysters) 2

Dried plant food 0 0 N/A 5 0 N/A Heterogeneous exposures (dates, plums, seaweed)

2

4.2.2 Storage 0 0 N/A 1 0 N/A <5 case-controls






Total n





4.2.3 Bottling, canning etc


4.2.5.1 Salt 0 0 N/A 2 0 N/A <5 case-controls 4.2.5.3 Salted/salty foods


4.2.5.3.1 Salted animal food Salted fish only:

Adulthood consumption 1 0 N/A 21 9 1.28 (1.13-1.44), times/week


Consumption, age 10 1 0 N/A 16 9 1.35 (1.14-1.60), times/week


Consumption, ages 0-3 0 0 N/A 10 5 1.42 (1.11-1.81), times/week


Mother’s consumption 0 0 N/A 3 0 N/A <5 case-controls Other salted animal

foods 0 0 N/A 10 0 N/A Heterogeneous exposures

(meat, fish, seafood, eggs) 2

4.2.5.3.2 Salted plant food

0 0 N/A 9 0 N/A Heterogeneous exposures (dates, plums, pulses)

2

4.2.6 Pickling 0 0 N/A 11 0 N/A Heterogeneous exposures (vegetables, fruits, spices )

2

4.2.7.1.1 Cured meats 0 0 N/A 2 0 N/A <5 case-controls 4.2.7.1.2 Smoked foods 0 0 N/A 4 0 N/A <5 case-controls 4.3 Processing 0 0 N/A 6 0 N/A Heterogeneous exposures

(meats, pork ) 2

4.3.1 Refining 0 0 N/A 6 0 N/A 1 ecological study; Heterogeneous exposures (bread, rice, noodles )

2

4.3.2 Hydrogenation 0 0 N/A 1 0 N/A <5 case-controls 4.3.3 Fermenting 1 0 N/A 10 0 N/A Heterogeneous exposures

(soy, fish, seafood, eggs) 2

4.3.5.1 Flavours 0 0 N/A 3 0 N/A <5 case-controls 4.3.5.4.1 Nitrites and nitrates

0 0 N/A 1 0 N/A <5 case-controls; 3 ecological studies






Total n





4.4.1 Fresh foods Fresh animal foods 0 0 N/A 6 0 N/A Heterogeneous exposures

(meat, fish, eggs, milk) 2

Fresh plant foods 0 0 N/A 9 0 N/A 1 ecological study; Heterogeneous exposures (vegetables, fruits, pulses)

2

4.4.1.1 Raw 0 0 N/A 2 0 N/A <5 case-controls 4.4.2 Cooked food 0 0 N/A 2 0 N/A <5 case-controls 4.4.2.1 Steaming, boiling, poaching


4.4.2.2 Stewing, casseroling


4.4.2.5 Frying 0 0 N/A 1 0 N/A <5 case-controls 4.4.2.6 Grilling and BBQ


5.3 Protein 0 0 N/A 1 0 N/A <5 case-controls 5.5.1 Vitamin A 0 0 N/A 1 0 N/A <5 case-controls 5.5.2 Non-provitamin A carotenoids


5.5.9 Vitamin C 0 0 N/A 3 0 N/A <5 case-controls 5.5.10 Vitamin D and calcium

0 0 N/A 1 0 N/A <5 case-controls; 1 ecological study; 1 cross-sectional study

5.5.11 Vitamin E 0 0 N/A 1 0 N/A <5 case-controls 5.5.13 Other vitamins 0 0 N/A 1 0 N/A <5 case-controls 5.6.2 Iron 0 0 N/A 3 0 N/A <5 case-controls 5.6.3 Calcium (and vitamin D)

0 0 N/A 1 0 N/A <5 case-controls; 1 ecological study; 1 cross-sectional study

5.6.4 Selenium 0 0 N/A 3 0 N/A <5 case-controls 5.6.5 Iodine 0 0 N/A 1 0 N/A <5 case-controls 5.6.6 Other minerals

Chromium 0 0 N/A 2 0 N/A <5 case-controls Copper 0 0 N/A 4 0 N/A <5 case-controls

Manganese 0 0 N/A 3 0 N/A <5 case-controls






Total n





Zinc 0 0 N/A 4 0 N/A <5 case-controls Other minerals 0 0 N/A 2 0 N/A <5 case-controls

1 June, 2006

# Changed referent group to lowest intake measured ‡ Derived RR using STATA 8.0

1

Results Tables Table of contents

1.2 Socio-economically defined diets ........................................................................................................................................................................4 1.3 Culturally defined diets .......................................................................................................................................................................................4 1.5 Other dietary patterns .........................................................................................................................................................................................4 1.6.2 Child ..................................................................................................................................................................................................................5 1.7 Other issues...........................................................................................................................................................................................................5 2.1.1 Cereals (grains).................................................................................................................................................................................................6 2.1.1.1 Wholegrain cereals and cereal products ........................................................................................................................................................7 2.1.1.2 Refined cereals and cereal products ...............................................................................................................................................................7 2.1.1 Starchy roots, tubers and plantains..............................................................................................................................................................10 2.2 Fruit and vegetables...........................................................................................................................................................................................10 2.2.1 Non-starchy (and starchy) vegetables ..........................................................................................................................................................11 2.2.1.1 Non-starchy root vegetables and tubers.......................................................................................................................................................19 2.2.1.2 Cruciferous vegetables...................................................................................................................................................................................22 2.2.1.3 Allium vegetables ...........................................................................................................................................................................................28 2.2.1.4 Green leafy vegetables ...................................................................................................................................................................................28 2.2.1.5 Other non-starchy vegetables .......................................................................................................................................................................32 2.2.1.6 Raw vegetables ...............................................................................................................................................................................................39 2.2.2 Fruits (general) ...............................................................................................................................................................................................40 2.2.2.1 Citrus fruits ....................................................................................................................................................................................................42 2.2.2.2 Other fruits .....................................................................................................................................................................................................45 2.3 Pulses (legumes)..................................................................................................................................................................................................55 2.4 Nuts and seeds ....................................................................................................................................................................................................62 2.5.1 Meat .................................................................................................................................................................................................................63 2.5.1.1 Fresh Meat ......................................................................................................................................................................................................67 2.5.1.2 Processed meat ...............................................................................................................................................................................................69 2.5.1.3.1 Beef ..............................................................................................................................................................................................................71 2.5.1.3.2 Pork .............................................................................................................................................................................................................72 2.5.1.3.4 Organ meats................................................................................................................................................................................................74 2.5.1.4 Poultry.............................................................................................................................................................................................................77 2.5.2 Fish ..................................................................................................................................................................................................................78 2.5.2.1 Salted Fish.......................................................................................................................................................................................................79

1 June, 2006


2

2.5.2.2 Other preserved fish (excluding salted fish) ................................................................................................................................................91 2.5.3 Shellfish and other seafood............................................................................................................................................................................95 2.5.4 Eggs .................................................................................................................................................................................................................99 2.6 Fats, oils and sugars as foods ..........................................................................................................................................................................104 2.6.1 Animal fats (as foods) ..................................................................................................................................................................................105 2.6.2 Plant oils (as foods) ......................................................................................................................................................................................106 2.6.4 Sugars ............................................................................................................................................................................................................108 2.7 Milk and dairy products..................................................................................................................................................................................108 2.8 Herbs, spices, condiments................................................................................................................................................................................109 2.9 Composite foods ...............................................................................................................................................................................................116 3.1 Total fluid intake ..............................................................................................................................................................................................122 3.2 Water .................................................................................................................................................................................................................122 3.3 Milk as beverage...............................................................................................................................................................................................123 3.5 Fruit juices ........................................................................................................................................................................................................124 3.6 Hot drinks .........................................................................................................................................................................................................125 3.6.1 Coffee.............................................................................................................................................................................................................125 3.6.2 Tea .................................................................................................................................................................................................................126 3.6.2.2 Green tea .......................................................................................................................................................................................................128 3.7 Alcoholic drinks................................................................................................................................................................................................128 3.7.1 Total alcoholic drinks ..................................................................................................................................................................................129 3.7.1.1 Beers ..............................................................................................................................................................................................................134 3.7.1.2 Wines .............................................................................................................................................................................................................135 3.7.1.3 Spirits ............................................................................................................................................................................................................135 3.7.1.4 Other alcoholic drinks .................................................................................................................................................................................136 4.1.2 Chemical contaminants ...............................................................................................................................................................................137 4.1.2.7.1 Cadmium...................................................................................................................................................................................................137 4.1.2.7.2 Arsenic.......................................................................................................................................................................................................138 4.1.2.7.3 Other heavy metals ..................................................................................................................................................................................139 4.1.2.9 Other contaminants .....................................................................................................................................................................................142 4.2 Preservation (preserved foods) .......................................................................................................................................................................143 4.2.1 Drying (dried foods) .....................................................................................................................................................................................158 4.2.2 Storage...........................................................................................................................................................................................................166 4.2.3 Bottling, canning, vacuum packing ............................................................................................................................................................167 4.2.5.1 Salt .................................................................................................................................................................................................................167 4.2.5.3 Salted foods ...................................................................................................................................................................................................167

1 June, 2006


3

4.2.5.3.1 Salted animal food....................................................................................................................................................................................168 4.2.5.3.2 Salted plant food.......................................................................................................................................................................................185 4.2.6 Pickling (pickled foods) ...............................................................................................................................................................................192 4.2.7.1.1 Cured meats ..............................................................................................................................................................................................197 4.2.7.1.2 Smoked foods ............................................................................................................................................................................................198 4.3 Processing .........................................................................................................................................................................................................199 4.3.1 Refining .........................................................................................................................................................................................................202 4.3.2 Hydrogenation ..............................................................................................................................................................................................204 4.3.3 Fermenting....................................................................................................................................................................................................205 4.3.5.1 Flavours.........................................................................................................................................................................................................213 4.3.5.4.1 Nitrites and nitrates .................................................................................................................................................................................214 4.4.1 Fresh food .....................................................................................................................................................................................................216 4.4.1.1 Raw ................................................................................................................................................................................................................230 4.4.2 Cooked food ..................................................................................................................................................................................................231 4.4.2.1 Steaming, boiling, poaching ........................................................................................................................................................................231 4.4.2.2 Stewing, casseroling .....................................................................................................................................................................................232 4.4.2.5 Frying ............................................................................................................................................................................................................232 4.4.2.6 Grilling (broiling) and barbecuing .............................................................................................................................................................233 5.3.1 Total protein .................................................................................................................................................................................................233 5.5.1 Vitamin A......................................................................................................................................................................................................234 5.5.1.2 Provitamin A carotenoids..............................................................................................................................Error! Bookmark not defined. 5.5.1.2.1 Beta-carotene ............................................................................................................................................................................................234 5.5.9 Vitamin C......................................................................................................................................................................................................235 5.5.10 Vitamin D (and calcium) .............................................................................................................................................................................235 5.5.11 Vitamin E ......................................................................................................................................................................................................236 5.5.13 Other vitamins (including multivitamins) .................................................................................................................................................237 5.6.2 Iron ................................................................................................................................................................................................................237 5.6.3 Calcium (and vitamin D) .............................................................................................................................................................................238 5.6.4 Selenium ........................................................................................................................................................................................................239 5.6.5 Iodine .............................................................................................................................................................................................................240 5.6.6 Other minerals..............................................................................................................................................................................................240

1 June, 2006


4

1.2 Socio-economically defined diets Case-control (1) Study identifier

Author, Yr

Exposure Exposure range

Assess-ment

Tool

Country Ethnicity

of subjects

No of subjects analysed

Age/ Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS02182

Armstrong

1983

Childhood history of poorer, simpler diet (mostly rice)

Yes or no Hospital records

Malaysia Chinese N/A Mixed 87 79 2 4.3 Popula-tion

N/A .01 N/A Sex, area of residence, ethnicity/ race, age, salted fish intake

1.3 Culturally defined diets Case-control (1) Studyy identiier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04944

Armstrong

1978

Multi-ethnic cuisine

Single v. multi-ethnic

Recall: interview

Malaysia Chinese 210 25-81/ Mixed

N/A N/A 2 0.2 single N/A < .01 N/A Unadjusted

1.5 Other dietary patterns Case-control (3)

1 June, 2006


5

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

Age stopped bottlefeeding

Never to 24+ months

FFQ - Study-specific

Singapore Chinese 606 Max 44/ Mixed

64 102 4 OR = 1.6 Never 0.6-5.5

N/A .01 Age, sex, education, ethnicity/ race

NAS01381

Jeannel

1990

Adult diet for weaning

Yes or no FFQ - Study-specific

Tunisia Tunisian 240 N/A/ Mixed

80 160 2 OR = 5.1 No N/A 0.03 N/A Sex, age, lifestyle factors, area of residence

NAS01459

Yu

1989

Age at which first solid food was given

N/A FFQ - Study-specific

China Chinese 612 Max 49/ Mixed

306 306 N/A Median = 6 months for both

N/A N/A Not signif-icant

N/A Area of residence, age, sex

1.6.2 Breastfeeding-Child Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Breast-feeding duration

Never to > 24 months


Algeria N/A 144 9-70/ Mixed

122 122 6 4.0 Never 1.24-12.8

0.02 N/A Area of residence, age, sex

NAS01056

Lee

1994

Breast-feeding duration

Never to 7+ months



64 103 3 0.6 Never 0.2-1.4

N/A .03 Age, sex, ethnicity/ race, education

1.7 Other diet pattern issues Case-control (1) Study Exposure Exposure Assess- Country Ethnicity No of Age/Sex of No. No. No. OR Ref CI P value p value Adjusted

1 June, 2006


6

identifier

Author, Yr

range ment

Tool

of subjects

subjects analysed

subjects cases controls categories group for trend

for

NAS04944

Armstrong

1978

Patterns of meals and snacks

N/A Recall: interview


N/A N/A N/A N/A N/A N/A Not signif-icant

N/A Un-adjusted

2.1.1 Cereals (grains) Total Cereals: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/ Sex of sub jects

No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Cereals (grains) Consume few to consume every day

Question-naire

China Chinese 416 N/A/ Mixed

208 208 4 16 Consume few

3.11- 82.42

N/A N/A Unadjusted

NAS06024

Huang

1997

Cereals: exposed 3 years before disease dx, include corn, wheat, cases and control were from Heilongjiang province

Yes vs No Question-naire


104 104 2 1.526 No 1.02-2.28

0.039 N/A Age, Sex, Chronic otolaryngological diseases, Area of residence, Consumption of vegetables, Use coal as fuel

Total Cereals: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


7

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Foods for chewing when teething: cherchem (wheat or barley pieces that have softened through contact w/ the floor and walls when these cereals are stored underground)

Ever vs Never


Algeria Un-known

144 9-70/ Mixed

72 72 2 4.0 Ever 0.18-4.4

N/A N/A Age, Sex, Area of residence

NAS01381

Jeannel

1990

Mhammas (cracked wheat), consumption during childhood

Less than once a month to 2+ times/ week


Tunisia Tunisian 240 Mean 41/ Mixed

80 160 3 0.3 Less than once a month

N/A N/A N/A Age, Sex, Area of residence, Living condition score

2.1.1.1 Wholegrain cereals and cereal products Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06022

Wang

1993

Whole-grain cereals

Not frequent or frequent

Question-naire

China Chinese 244 13-70/ Mixed

122 122 2 0.186 Not frequent

N/A .0235 N/A Sex, age, environmental factors, plant oil, pork fat, salted fish, non-nutrient chemicals, high-income, vegetable intake, coloured vegetables

2.1.1.2 Refined cereals and cereal products Bread: Adulthood consumption Case-control (3)

1 June, 2006


8

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value p value for trend

Adjusted for

NAS01459

Yu

1989

Bread, consumption at age 3 years prior to diagnosis



306 306 N/A N/A N/A N/A Not significant

N/A Age, Sex, Area of residence

NAS01812

Geser

1978

Bread eaten often, by household of cases and controls

Yes vs No FFQ - Study-specific


147 147 2 0.43 No 0.27-0.7

N/A N/A Age, Sex

NAS04944

Armstrong

1978

Bread, for breakfast among families of participants

N/A Recall Malaysia Chinese 210 25-81/ Mixed

60 150 N/A OR > 1

N/A N/A Signif-icant

N/A Unadjusted

Bread: Childhood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00424

Laouamri

2001

Foods for chewing when teething: crust of bread

Ever vs Never


Algeria Un-known

144 9-70/ Mixed

72 72 2 OR = 1

Ever N/A N/A N/A Age, Sex, Area of residence

NAS01459

Yu

1989

Bread, consumption at age 10





NAS01520

Yu

1988

Bread, consumed by subject at age 10


China Chinese 302 Mean 35/ Mixed


N/A Age, Sex

Noodles Case-control (1)

1 June, 2006


9

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04944

Armstrong

1978

Noodles in three main daily meals combined, among cases and controls


60 150 N/A 1.2 N/A N/A Not signif-icant

N/A Ethnicity/ Race, Census district, Household type, Socio-economic status, Sex, Age

Rice Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04944

Armstrong

1978

Rice, for breakfast; families of participants


60 150 N/A OR > 1


N/A Unadjusted

NAS04944

Armstrong

1978

Plain rice, at evening meal; families of participants


60 150 N/A OR < 1


N/A Unadjusted

NAS04944

Armstrong

1978

Rice porridge, at evening meal among families of participants


60 150 N/A OR > 1


N/A Unadjusted

NAS06024

Huang

1997

Rice, exposed at age 10, specific on rice cases and control were from Heilongjiang province



104 104 2 0.707 No 0.505-0.92

0.044 N/A Unadjusted

Ecological (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

r2 Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


10

NAS00817

Koo

1997

Rice Per capita consumption

Food survey

China, Hong Kong

Chinese N/A Male N/A N/A Continuous 0.86 N/A N/A .001 N/A age

NAS00817

Koo

1997


Food survey

China, Hong Kong

Chinese N/A Female N/A N/A Continuous 0.85 N/A N/A .034 N/A age

2.1.2 Starchy roots, tubers and plantains Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00424

Laouamri

2001

Baby foods: mashed potatoes

<3 times to >7 times a week



56 58 3 2.0 <3 times a week

0.06-59.7

Not signif-icant

N/A Sex, age, area of residence

NAS06023

Zou

1999

Taro None to high Question-naire


101 199 5 0.76 none 0.46-1.26

0.29 N/A Unadjusted

NAS06023

Zou

1999

Sweet potatoes

None to high Question-naire


100 199 5 0.67 none 0.33-1.36

0.25 N/A Unadjusted

2.2 Fruit and (non-starchy) vegetables

Case-control (1) Study identifier

Author, Yr


Asses-sment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

1 June, 2006


11

Study identifier

Author, Yr


Asses-sment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01381

Jeannel

1990

Fruits and vegetables



80 160 2 N/A N/A N/A Not signif-icant

N/A Age, sex, area of residence

2.2.1 Non-starchy vegetables Total non-preserved vegetables: Adulthood consumption Case-control (5) Meta-analysis Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: vegetable

Lowest to Highest

Dietary History question-naire


375 327 4 0.6 Lowest 0.4-1.0

Not Signif-icant

N/A Age, Sex, Ethnicity/ Race, Subjects w/ mothers questionnaire, Total calories

NAS00577

Yuan

2000

All fresh vegetables

≤ 538 times per year to > 866 times per year



935 1032 4 0.85 ≤ 538 times per year

0.65-1.10

N/A 0.13 Sex, Age, Education, Smoking, Exposure to smoke from heated rapeseed oil and burning coal while cooking, occupational exposure to chemical fumes, History of chronic ear and nose condition

NAS01922

Ning

1990

Fresh vegetable, consumption 3 years prior to diagnosis




N/A Age, Sex, Area of Residence

1 June, 2006


12

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS06003

Ye

1995

Non-starchy vegetables

≤15.75 times per month to > 15.75 times per month



135 135 2 0.51 ≤15.75 times per month #

0.29-0.88

<0.05 N/A Age, Sex, Area of residence

NAS06022

Wang

1993


less consumed vs frequently consumed

Question-naire


122 122 2 0.256 Less consumed

N/A 0.0051 N/A Age, Sex, high-income, Non nutrient chemicals, Consumption of salted fish, pork fat, whole grains, plant oil, and vegetables, smoking in living area


Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Regression slope

Ref group

CI P value

p value for trend

Adjusted for

NAS00817

Koo

1997

Fresh vegetables

N/A Per capita consumption

China, Hong Kong

Chinese N/A Male N/A N/A Continuous r2 = -0.77 N/A N/A 0.009 N/A age

NAS00817

Koo

1997

Fresh vegetables


China, Hong Kong

Chinese N/A Female N/A N/A Continuous r2 = -0.75 N/A N/A 0.013 N/A age

NAS06029

Guo

2001


N/A Interview of local residents

China Chinese N/A Mixed N/A N/A Continuous Regression slope =2.36

N/A N/A N/A N/A N/A

Total non-preserved vegetables: Childhood/Infancy consumption Case-control (2)

1 June, 2006


13

Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Intake for Age 10: Non-specific vegetables

0-4 servings to >4 servings

Dietary History questionnaire


91 114 2 0.4 0-4 servings

0.1-1.0

N/A N/A Age, Sex, Ethnicity/Race

NAS00531

Ward

2000

Intake for Age 3: Non-specific vegetables

0-4 servings to >4 servings



87 110 2 0.5 0-4 servings

0.3-1.1

N/A N/A Age, Sex, Ethnicity/ Race

NAS00531

Ward

2000

During Weaning: Non-specific vegetables

None to > 4 servings



84 111 3 0.6 None 0.3-1.3


NAS00531

Ward

2000

Mother's diet during breastfeeding: Fresh vegetables

Highest vs lowest



375 327 N/A 0.3 Lowest 0.1-1/5

N/A N/A N/A

NAS01922

Ning

1990

Fresh vegetable, consumption at 10 years of age





Green vegetables: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00700

Farrow

1998

Labeled dark green vegetables (broccoli, cauliflower, spinach, mustard or turnip greens, coleslaw)

Lowest to highest

FFQ – Block

United States

Unknown 345 18-74/ Mixed

129 206 4 0.99 Lowest 0.51-1.94

N/A 0.60 Age, Sex, Energy Intake, Alcohol consumption, Smoking Habits

1 June, 2006


14

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Other green vegetables (green onions, broccoli, chives, watercress, Chinese lettuce), 5 years pre-diagnosis

Monthly to greater than weekly


Malaysia Chinese 564 Mean 45/ Mixed

282 282 3 0.5 Monthly 0.23-1.07

N/A 0.026 Unadjusted

NAS00825

Chen

1997

Green pepper, chives, celery, 3 years ago



104 104 Continuous 0.63 N/A 0.44-0.91

N/A N/A Age, Sex, Area of Residence

NAS06024

Huang

1997

Exposed 3 years before disease diagnosed (green pepper, celery, cases and control were from Guangdong province)

Yes vs no Question-naire


208 208 2 0.63 No 0.44-0.91


Green vegetables: Childhood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Other green vegetables (green onions, broccoli, chives, watercress, Chinese lettuce), consumption at age 10

Monthly to greater than weekly



282 282 3 0.59 Monthly 0.33-1.06

N/A N/A Unadjusted

NAS00825

Chen

1997

Green peppers, chives, celery, 10 years old



104 104 Contin-uous

0.54 N/A 0.38-0.78


1 June, 2006


15

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

Fresh green vegetables, consumption during weaning



306 306 2 0.6 No 0.3-1.1


NAS01459

Yu

1989

Fresh green vegetables, consumption during ages 1-2

Rarely to weekly



110 139 3 1.7 Weekly 0.6-4.9

N/A Not Signif icant

Age, Sex, Area of Residence

NAS01459

Yu

1989

Fresh green vegetables, consumption at age 10

Less than daily to daily



306 306 2 1.3 Daily 0.3-5.1


Other non-preserved vegetables Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS04944

Armstrong

1978

Vegetables, for breakfast among families of participants


60 150 N/A OR < 1

N/A N/A Signif- icant

N/A Unadjusted

NAS04944

Armstrong

1978

Fresh vegetables, at evening meal among families of participants


60 150 N/A OR < 1


N/A Unadjusted

NAS04944

Armstrong

1978

Vegetables in three main daily meals combined, among cases and controls


60 150 N/A 0.9 N/A N/A N/A N/A Age, Sex, Census district, Household type, Race/ ethnicity, SES

1 June, 2006


16

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS06022

Wang

1993

Colored vegetables

less consumed vs frequently consumed

Question-naire



N/A 0.0108 N/A Age, Sex, high-income, Non nutrient chemicals, Consumption of salted fish, pork fat, whole grains, plant oil, and vegetables, Has smoking in living area

Total preserved vegetables: Adulthood consumption Case-control (7) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: Preserved vegetables

Ever vs Never



375 327 2 N/A N/A N/A Not Signif-icant


NAS00577

Yuan

2000

All preserved vegetables (salted mustard green/ bok choi/ stem vegetables, pickled stem vegetable/ cucumber, salted root and preserved root)

≤40 times per year to > 200 times per year

FFQ - Study-specifi


935 1032 4 1.43 ≤40 times per year

1.11-1.86

N/A 0.001 Sex, Age, Educational Level, Smoking, Exposure to smoke from heated rapeseed oil and burning coal while cooking, Occupational exposure to chemical fumes, History of chronic ear and nose condition

1 June, 2006


17

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

Canned salted or pickled vegetables, consumption during adulthood

Never exposed to more than 3 times per month



199 405 4 4.9 Never 1.8-12.9

N/A 0.004 Age, Sex, Education level, Dialect Group

NAS01113

Zheng

1994

Salted, dried, or tinned vegetables in brine




N/A N/A

NAS01190

Zheng

1993

Salted vegetables



205 205 N/A >1.0 N/A N/A Signif- icant

N/A N/A

NAS01922

Ning

1990

Dried vegetable, consumption 3 years prior to diagnosis





NAS01922

Ning

1990

Salted vegetable, consumption 3 years prior to diagnosis





NAS01922

Ning

1990

Pickled vegetable, 3 years prior to diagnosis





NAS06002

Duan

2000

Pickled vegetables

N/A Question-naire


100 100 Continuous r2 = 0.015


N/A Environmental Factors, Gas Range, Pungent foods, SES

Total preserved vegetables: Childhood/Infancy consumption Case-control (4)

1 June, 2006


18

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Preserved vegetables Intake for Age 10

None to >59.2 grams



89 113 4 0.9 None 0.3-2.6


NAS00531

Ward

2000

Intake for Age 3: Preserved vegetables

None to > 44.8 grams



88 103 4 0.9 None 0.3-2.4


NAS00531

Ward

2000

During Weaning: Preserved vegetables

None to > 0 Dietary History question-naire


87 112 2 1.3 None 0.6-2.5


NAS00531

Ward

2000

Mother's diet during breastfeeding: Preserved vegetables

Highest vs lowest



375 327 N/A 0.6 Lowest 0.2-1/5

N/A N/A N/A

NAS01056

Lee

1994

Canned salted or pickled vegetables, at age 10




149 344 4 0.5 Never 0.1-1.4


NAS01381

Jeannel

1990

Dietary Intake During Weaning: Consumption of Pickled Vegetables

Less than once a month to more than 2 a week




N/A N/A N/A Age, Sex, Area of Residence, Living condition score

NAS01922

Ning

1990

Dried vegetable, consumption at 10 years of age





1 June, 2006


19

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

Salted vegetable, consumption at 10 years of age





NAS01922

Ning

1990

Pickled vegetable, at age 10





2.2.1.1 Non-starchy root vegetables and tubers Total Root Vegetables Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00424

Laouamri

2001

Non-starchy root vegetables/tubers, Foods for chewing when teething

Ever vs Never



72 72 2 1.0 N/A N/A Not Signif- icant


Carrots: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00825

Chen

1997

Carrots, 3 years ago



104 104 N/A N/A N/A N/A Not Signif- icant


1 June, 2006


20

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

Carrots, consumption 3 years prior to diagnosis

Never to Weekly



100 300 4 0.8 Never 0.3-1.9

N/A 0.3 Age, Sex, Area of Residence

Carrots: Childhood consumption Case-control (6) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Baby Foods: Carrots

< 3 times per week to > 7 times a week



72 72 3 0.3 N/A 0.1-0.87

0.05 N/A Age, Sex, Area of Residence

NAS00825

Chen

1997

Carrot, 10 years old





NAS01459

Yu

1989

Carrots, consumption at age 10

Rarely to weekly



306 306 2 0.2 Rarely 0.1-0.3


NAS01520

Yu

1988

Carrots, consumed by subject at age 10



128 174 N/A N/A N/A N/A Not signif-icant

N/A Age, sex

NAS01922

Ning

1990

Carrots, consumption at 10 years

Never to Weekly



100 300 4 0.4 Never N/A 0.09 N/A Age, Sex, Area of Residence, salted fish consumption and salted shrimp paste consumption at 10 years

1 June, 2006


21

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Carrot, exposed at age of 10, cases and control were from Guangdong province



104 104 2 0.6 No 0.41-0.99


Preserved Root Vegetables Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS06023

Zou

1999

Salted root vegetables

< 9 times a month to ≥ 9 times a month

Question-naire


97 192 2 2.2 < 9 times a month

1.3-3.6


NAS06024

Huang

1997

Pickled root vegetables, exposed at age of 10, cases /control were from Guangdong province



104 104 2 0.75 No 0.57-0.99


NAS06024

Huang

1997

Preserved root vegetables exposed at age of 10, cases and control were from Guangdong province



104 104 2 1.81 No 1.01– 3.33

0.045 N/A Age, Sex, No Separate Kitchen, Grapes, and dired orange, Family history of cancer

NAS06024

Huang

1997

Preserved other root vegetables

consume few to consume every week

Question-naire


104 104 3 2.42 Consume few

0.99-5.92

N/A N/A Unadjusted

1 June, 2006


22

2.2.1.2 Cruciferous vegetables Cabbage: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Fresh Bok Choi (chinese white cabbage)

Less than weekly to daily



935 1032 3 0.97 Weekly 0.81-1.17

N/A 0.85 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition

NAS00749

Armstrong

1998

Chinese flowering cabbage, 5 years pre-diagnosis

Less than weekly to weekly



282 282 2 0.64 Less than weekly

0.4-1.04


NAS00749

Armstrong

1998

Chinese flowering cabbage, lifetime, trichotomous categories at age 10 and age 5 years prior to diagnosis

Less than monthly to monthly or more



282 282 2 0.5 Less than monthly

N/A 0.0004 N/A salted fish, recent consumption, salted egg/ oranges/ tangerines/ shrimp, lifetime consumption, pork/beef liver / beer consumption, SES

NAS06024

Huang

1997

Cabbage: exposed 3 years before disease: cases and control were from Guangdong province



104 104 2 0.628 No 0.44-0.9


Non-Preserved Cruciferous Vegetables: Adulthood consumption Case-control (5)

1 June, 2006


23

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Chinese kale, 5 years pre-diagnosis

Monthly to more than weekly



282 282 3 0.63 Monthly 0.39-1.01


NAS00825

Chen

1997

Chinese cabbage and rutabaga, 3 years ago



104 104 Continuous 0.63 N/A 0.44-0.9


NAS01056

Lee

1994

turnip root, consumption during adulthood



Singa-pore

Chinese 606 Max 44/ Mixed

200 405 4 1.0 Never 0.1-5.6


NAS01922

Ning

1990

mustard, consumption 3 years prior to diagnosis





NAS06024

Huang

1997

Cauliflower Less than once a month to every day

Question-naire


104 104 4 1.048 No 0.36-3.05

N/A N/A Unadjusted

Non-Preserved Cruciferous Vegetables: Childhood consumption Case-control (6) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Chinese flowering vegetable, consumption at age 10

Less than weekly to weekly




0.29-0.77

N/A N/A Unadjusted

1 June, 2006


24

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Chinese kale, consumption at age 10




282 282 3 0.71 Monthly 0.4-1.27

N/A N/A Unadjusted

NAS00825

Chen

1997

Chinese cabbage, rutabaga, 10 years old



104 104 N/A N/A N/A N/A Not Signif icant


NAS01056

Lee

1994

turnip root, consumption at age 10 years



Singa-pore


145 344 4 1.2 Never 0.4-3.4


NAS01922

Ning

1990

mustard, consumption at 10 years of age





NAS60010

Cai

1996

leaf mustard, consumed around 1978 and >=3 times/ week

< 12 times per month to ≥ 12 times per month



115 115 2 1.918 < 12 times per month

1.456-2.527

0.000 N/A Age, Sex, Area of Residence, family cooking fuel, fresh green vegetables, history of chronic nasopharyngeal diseases

NAS60010

Cai

1996

leaf mustard, consumed around 1968 and >=3 times/ week




115 115 2 1.443 < 12 times per month

1.158-1.8


NAS06024

Huang

1997

cauliflower, exposed at age of 10, cases / controls were from Heilongjiang province



104 104 2 0.697 No 0.52-0.94

0.019 N/A Age, Sex, Area of Residence, chronic otolaryngological diseases, use coal as fuel, rice, wheat, and corns

1 June, 2006


25

Preserved Cruciferous Vegetables: Adulthood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

Pickled chinese cabbage, 3 years ago





NAS01056

Lee

1994

tang chye, a type of preserved cabbage, consumption during adulthood



Singa-pore


199 406 5 1.5 Never 0.6-3.4

N/A N/A Age, Sex, Education level, Dialect Group

NAS01056

Lee

1994

chye poh, preserved Chinese radish, consumption during adulthood



Singa-pore


200 406 4 2.8 Never 1.2-6.0


NAS01056

Lee

1994

kiam chye, salted mustard greens, consumption during adulthood

Never exposed to 1-3 times per week


Singa-pore


200 406 4 3.1 Never 1.4-6.5


NAS01608

Yu

1986

salted mustard green (mui choi), subject's consumption at 10 years of age or 3 years prior to diagnosis




N/A Age, sex, salted fish intake

NAS01922

Ning

1990

sour cabbage, consumption 3 years prior to diagnosis





1 June, 2006


26

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06003

Ye

1995

Pickled leaf mustard Less than 4.2 times per month to greater than 75 times per month

Dietary history question-naire


135 135 3 6.11 ≤ 4 .2 times per month

N/A < 0.01 N/A Age, Sex, Area of residence

NAS06003

Ye

1995

pickled radish <75 times per month to ≥ 75 times per month



135 135 2 1.75 ≤ 75 times per month

1.1-2.79

< 0.05 N/A Age, Sex, Area of residence

Preserved Cruciferous Vegetables: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

Pickled Chinese Cabbage, 10 years old



104 104 Continuous 0.75 N/A 0.57-0.99


NAS01056

Lee

1994

tang chye, a type of preserved cabbage, consumption at age 10 years

Never exposed to more than 3 times per week


Singa-pore


147 342 5 0.8 Never 0.2-2.6


NAS01056

Lee

1994

chye poh, preserved Chinese radish, consumption at age 10 years



Singa-pore


150 342 4 1.0 Never 0.4-2.1


NAS01056

Lee

1994

kiam chye, salted mustard greens, consumption at 10 years old



Singa-pore


148 344 4 1.1 Never 0.4-2.6


1 June, 2006


27

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01520

Yu

1988

salted mustard greens, consumed by subject during weaning

Yes vs no FFQ - Study-specific


128 174 2 5.4 No 1.2-23.8

0.06 N/A Age, sex

NAS01520

Yu

1988

salted mustard green, consumed by subject between ages 1 to 2 years

Rarely to weekly



128 174 3 1.6 Rarely 0.5-4.7

0.06 N/A Age, sex

NAS01520

Yu

1988

salted mustard green, consumed by subject at age 10

Rarely to weekly



128 174 3 1.3 Rarely 0.3-6.7

Not signif-icant

Not signif-icant

Age, sex

NAS01520

Yu

1988

salted cabbage, consumed by subject at age 10




N/A Age, sex

NAS01520

Yu

1988

salted radish, consumed by subject at age 10




N/A Age, sex

NAS01520

Yu

1988

pickled cabbage, consumed by subject at age 10




N/A Age, sex

NAS01520

Yu

1988

salted mustard green, consumed by subject during weaning

Rarely to monthly




N/A Age, sex

NAS01922

Ning

1990

sour cabbage, consumption at 10 years of age





1 June, 2006


28

2.2.1.3 Allium vegetables Case-control (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

RR/OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

Garlic, at age 10 or adult





2.2.1.4 Green leafy vegetables (excluding cruciferous vegetables) Total Green Leafy Vegetables: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Other dark green leafy vegetable (not bok choi) fresh





0.73-2.14


NAS01113

Zheng

1994

Leafy Vegetables, in the year before diagnosis

Monthly to Daily



88 176 3 0.1 Monthly N/A 0.008 N/A Age, sex, SES, area of residence

NAS06003

Ye

1995

Green leafy vegetables (not cruciferous)

<12.5 times/ month to ≥75.8 times/month



135 135 3 0.29 <12.5 times/ month #

N/A <0.01 N/A Age, Sex, Area of residence

1 June, 2006


29

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Green leafy vegetables, exposed 3 years before disease diagnosed, cases and control were from Guangdong province



104 104 2 1.733 No 1.19-2.53

.004 N/A Unadjusted

Total Green Leafy Vegetables: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01520

Yu

1988

fresh green leafy vegetables, during weaning




0.86 Age, sex

NAS01520

Yu

1988

fresh green leafy vegetables, between ages 1 to 2 years




0.92 Age, sex

NAS01520

Yu

1988

fresh leafy green vegetables, at age 10




N/A Age, sex

NAS60010

Cai

1996

Green leafy vegetables, consumed around 1968 and < 3 time/week

<12 times per month to ≥12 times per month



115 115 2 0.514 <12 times per month #

0.34-0.78

0.0016 N/A Age, Sex, Area of residence, history of other nasopharyngeal diseases, family cooking fuel, pickled foods

1 June, 2006


30

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS60010

Cai

1996

Green leafy vegetables, consumed around 1978 and < 3 time/week

<12 times per month to ≥12 times per month



115 115 2 0.444 <12 times per month #

0.29-0.67

0.000 N/A Age, Sex, Area of residence

Water spinach Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

water spinach, 5 years pre-diagnosis



Malaysia Chinese 564 N/A/ Mixed

282 282 3 0.72 Monthly 0.45-1.17


NAS00749

Armstrong

1998

water spinach, consumption at age 10




282 282 3 0.51 Monthly 0.28-0.93

N/A N/A Unadjusted

Preserved Green Leafy Vegetables: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Salted green leafy vegetables, 5 years pre-dx




282 282 3 3.33 Monthly 1.84-6.01


1 June, 2006


31

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

Mei chye (preserved greens and leafy vegetables), consumption in adulthood


Singa-pore



N/A Age, sex, ethnicity/ race, education, belachan, canned, salted, & pickled vegetables, vitamin C, salted soy beans, kiam chye, vitamin E

NAS01922

Ning

1990

dried kelp, 3 years prior to diagnosis





NAS01922

Ning

1990

dried seaweed, 3 years prior to diagnosis





Preserved Green Leafy Vegetables: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

Salted green leafy vegetables, at age 10




282 282 3 0.84 Monthly 0.45-1.58

N/A N/A Unadjusted

NAS01922

Ning

1990

dried kelp, at 10 years of age





NAS01922

Ning

1990

dried seaweed at 10 years of age





1 June, 2006


32

2.2.1.5 Other non-starchy vegetables Tomatoes: Adulthood consumption Case-control (5) Meta-analysis Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS00577

Yuan

2000

Tomatoes, fresh





N/A N/A 0.10 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition, oranges/ tangerines

NAS00749

Armstrong

1998

tomatoes, 5 years pre-diagnosis




282 282 3 0.5 Monthly 0.28-0.87


NAS01459

Yu

1989

tomatoes, unsure time of consumption



306 306 N/A N/A N/A N/A Signif-icant

N/A Age, sex, area of residence, salted fish, fermented fish sauce, moldy bean curd, chan pai mui, salted shrimp paste, gar ink gee

NAS06023

Zou

1999

tomatoes None to ≥ 9 times a month

Question-naire


102 201 3 2.59 None 0.69-9.72

0.36 N/A Unadjusted

NAS06030

Huang

2002

Tomatoes Less to frequently consumed

Question-naire



0.39-0.83


Tomatoes: Childhood consumption Case-control (3)

1 June, 2006


33

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

tomatoes, consumption at age 10




282 282 3 0.8 Monthly 0.48-1.32

N/A N/A Unadjusted

NAS01459

Yu

1989

tomatoes, during weaning



306 306 2 0.0 No 0.0-0.9

N/A N/A Age, sex, area of residence

NAS01459

Yu

1989

tomatoes, during ages 1-2

Rarely to weekly



110 138 3 0.3 Rarely 0.1-0.7

N/A <.05 Age, sex, area of residence

NAS01459

Yu

1989

tomatoes, at age 10

Rarely to daily



110 137 4 0.3 Rarely 0.1-1.3


NAS01520

Yu

1988

tomatoes, between ages 1 to 2 years



128 174 N/A N/A N/A N/A 0.38 (one sided)

N/A Age, sex

NAS01520

Yu

1988

tomatoes, at age 10




N/A Age, sex

Other Non-Preserved Vegetables: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


34

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Light green/ orange leafy vegetables, fresh





0.63-1.5


NAS00577

Yuan

2000

Gourds, fresh Less than weekly to daily




0.73-1.09


NAS00577

Yuan

2000

Green peppers, fresh





N/A N/A 0.43 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition, oranges/tangerines

NAS04944

Armstrong

1978

sliced raw chili, at evening meal among families of participants


60 150 N/A <1.0 N/A N/A Signif- icant

N/A Unadjusted

NAS04944

Armstrong

1978

sliced raw chili, in three main daily meals combined, among families of participants


60 150 N/A 0.8 N/A N/A <.01 N/A Unadjusted

NAS06003

Ye

1995

white color vegetables

≤ 3.3 times per month to > 3.3 times per month



135 135 2 0.30 ≤ 3.3 times per month #

0.18-0.51


1 June, 2006


35

Other Non-Preserved Vegetables: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS60010

Cai

1996

Yellow color, consumed around 1968




115 115 2 0.64 < 12 times per month #

0.45-0.91


NAS60010

Cai

1996

yellow color, consumed around 1978 and < 3 times /week




115 115 2 0.83 < 12 times per month #

0.44-0.91


NAS06024

Huang

1997

Green bean and eggppant, at age of 10, cases /control were from heilongjiang province



104 104 2 0.551 No 0.33-0.92


Total Preserved Vegetables: Adulthood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: vegetables in brine

Currently- twenty years ago



72 72 2 2.77 N/A 1.34-5.71


NAS00577

Yuan

2000

Preserved leafy vegetables (salted mustard green, salted bok choi, etc)

Less than monthly to daily




0.65-2.9


1 June, 2006


36

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Preserved Stem Vegetables (salted stem vegetables and pickled stem vegetable)





1.24-2.84

N/A <0.001 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition

NAS00577

Yuan

2000

Preserved root vegetables (salted root and preserved root)





0.7-1.53


NAS00825

Chen

1997

Salted vegetables, 3 years ago



104 104 N/A N/A N/A N/A Not signfi- icant


NAS01056

Lee

1994


Never exposed to 1-3 times per month


Singa-pore


200 406 4 2.8 Never 0.9-8.2


NAS06023

Zou

1999

Salted other non-starchy vegetables

None to ≥ 9 times a month

Question-naire


100 202 4 2.28 None 1.4-3.73


Total Preserved Vegetables: Childhood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


37

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

salted vegetables, 10 years old



104 104 Contin-uous

0.76 N/A 0.58-0.99


NAS01056

Lee

1994

Mei chye (preserved greens and leafy vegetables), at age 10 years



Singa-pore


150 341 4 1.3 Never 0.6-2.6


NAS06024

Huang

1997

Salted vegetables, exposed at age of 10, cases /control were from Guangdong province



104 104 2 0.755 No 0.58-1.0


Other Preserved Vegetables: Adulthood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasoning: salted dried tomatoes




72 72 2 7.5 N/A 3.09-18.2


NAS00749

Armstrong

1998

salted root, 5 years pre-diagnosis




282 282 3 2.19 monthly 1.33-3.62


NAS00825

Chen

1997

Plum vegetable (Chan Pai Mui), 3 years ago



104 104 Contin-uous

1.73 N/A 1.19-2.53


1 June, 2006


38

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

Plum vegetable Less than once a month to greater than once a week




1.04-6.19

N/A <0.05 Age, Sex, Area of Residence, Grape and Preserved Plum, No separate kitchen, Kitchen range without chimney

NAS01056

Lee

1994

sze chuan chye, a salted Chinese tuber, consumption during adulthood



Singa-pore


197 404 4 2.4 Never 1.1-5.2


NAS01381

Jeannel

1990

Intake During Preceding Year to Diagnosis: Fungus on Pickled Vegetables



80 160 2 3.3 No N/A 0.03 N/A Age, sex, area of residence, living condition score

Other Preserved Vegetables: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

salted root, at age 10




282 282 3 1.75 monthly 0.98-3.10

N/A N/A Unadjusted

NAS01056

Lee

1994

sze chuan chye, a salted Chinese tuber, consumption at age 10 years



Singa-pore


145 340 4 1.4 Never 0.4-4.5


1 June, 2006


39

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01381

Jeannel

1990

During Weaning: Fungus on pickled vegetables




NAS01520

Yu

1988


Rarely to daily



128 174 4 3.2 Rarely 0.6-17.6

0.03 (one sided)

N/A Age, sex

NAS01520

Yu

1988

chung choi, consumed by subject during weaning



128 174 Contin-uous

0.518 N/A N/A 0.021 (one sided)

N/A Age, sex, other household member smoked at birth, salted fish during pregnancy, salted duck egg/ salted mustard green during weaning, dried fish/ fermented soy paste during ages 1 and 2 yr

2.2.1.6 Raw vegetables Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

Raw green vegetables




282 282 3 0.5 Monthly 0.23-1.07

N/A .026 Unadjusted

NAS04944

Armstrong

1978

Sliced raw chili

At evening meals

Recall Malaysia Chinese 210 25-81/ Mixed

60 150 2 N/A N/A N/A Cases ate less at evening meals

N/A Unadjusted

1 June, 2006


40

2.2.2 Fruits (general) Total non-preserved fruits: Adulthood consumption Case-control (6) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS00700

Farrow

1998

Fruits, (apples, bananas, peaches, cantaloupe, watermelon, strawberries, oranges, grapefruit, juice, etc)

Lowest to highest

FFQ – Block

United States


129 206 4 0.87 Lowest 0.41-1.83


NAS01141

Zheng

1994

Fresh fruit, in the past 7 years




N/A N/A

NAS01922

Ning

1990

fresh fruit, 3 years prior to diagnosis





NAS04944

Armstrong

1978

Fresh fruit, at evening meal, families of participants



N/A Unadjusted

NAS06003

Ye

1995

Green color fruits less to more frequently



135 135 2 0.40 Consumed less #

0.36-0.61


NAS06030

Huang

2002

Fresh fruits Less to frequently consumed

Question-naire



0.44-1.04


1 June, 2006


41

Total non-preserved fruits: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00531

Ward

2000

Fruits: Childhood Dietary Intake for Age 3

None to ≥ 4.4 per month


China, Taiwan

Chinese 702 < 75/ Mixed

375 327 4 0.9 None 0.3-2.6

N/A N/A Age, sex, ethnicity/ race

NAS00531

Ward

2000

Fruits: Childhood Dietary Intake During Weaning

Less than 0.36 to ≥ 8 per month


China, Taiwan


375 327 4 2.1 Less than 0.36 per month

0.6-7.4


NAS00531

Ward

2000

Fruits: Mother's diet during breastfeeding

N/A Dietary History question-naire

China, Taiwan


375 327 3 0.5 None 0.2-1.5

N/A N/A N/A

NAS01141

Zheng

1994

Fresh fruit, ages 0-3




N/A N/A

NAS01141

Zheng

1994

Fresh fruit, age of 10




N/A N/A

NAS01922

Ning

1990

Fresh fruit, at age 10





NAS60010

Cai

1996

fresh fruit, consumed around 1968 and <3 times/ week

< 12 times / month to ≥ 12 times / month



115 115 2 0.67 < 12 times /month #

0.49-0.90


1 June, 2006


42

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS60010

Cai

1996

fresh fruit, consumed around 1978, < 3 time/week




115 115 2 0.68 < 12 times /month #

0.52-0.89


Preserved fruits Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Preserved fruits, 5 years pre-diagnosis

Less than monthly to more than weekly




0.71-2.85


NAS00749

Armstrong

1998

Preserved fruits, at age 10





0.82-2.75

N/A N/A Unadjusted

2.2.2.1 Citrus fruits Total citrus fruit: Adulthood consumption Case-control (5) Meta-analysis Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


43

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Oranges and tangerines, fresh





N/A N/A 0.0005 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition, green/red peppers, tomatoes, & green beans/peas

NAS00700

Farrow

1998

oranges, grapefruit, and orange juice

Lowest to highest

FFQ – Block

United States


129 208 4 0.68 Lowest 0.33-1.41

N/A 0.08 Age, Sex, Energy Intake, Alcohol, Smoking Habits

NAS00749

Armstrong

1998

Orange/ tangerine, 5 years pre-diagnosis





0.31-0.85


NAS00749

Armstrong

1998

oranges/ tangerines lifetime, dichotomous categories at age 10 and age 5 years prior to diagnosis





N/A 0.025 N/A SES, Salted fish, recent consumption, salted egg/ shrimp / Chinese flowering cabbage, lifetime consumption, pork/ beef liver/ beer consumption

NAS00825

Chen

1997

Tangerine/ orange, 3 years ago

Regression model



104 104 Contin-uous

0.66 N/A 0.5-0.89


1 June, 2006


44

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Citrus fruits, exposed 3 years before disease diagnosed, cases / control from Guangdong province



104 104 2 0.664 No 0.5-0.89


NAS06024

Huang

1997

Citrus fruits, exposed 3 years before disease diagnosed cases / control were from Heilongjiang province



104 104 2 0.628 No 0.41-0.95


Total citrus fruit: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

orange/ tangerine, consumption at age 10





0.51-1.86

N/A N/A Unadjusted

NAS00825

Chen

1997

Tangerine/ orange, age 10





NAS01459

Yu

1989

oranges/ tangerines ages 1-2

Rarely to weekly



110 139 3 0.3 Rarely 0.1-0.9


1 June, 2006


45

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

oranges/ tangerines at age 10

Rarely to weekly



110 139 3 1.2 Rarely 0.5-2.9

N/A Not significant

Age, sex, area of residence

NAS01520

Yu

1988

oranges / tangerines ages 1-2



128 174 N/A N/A N/A N/A 0.86 N/A Age, sex

NAS01520

Yu

1988

oranges / tangerines at age 10




N/A Age, sex

Preserved citrus fruits Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Preserved orange, cases and control were from Guangdong province

Yes vs No

Question-naire


104 104 2 2.95 No 1.04-8.41

0.043 N/A Age, Sex, No separate kitchen, dried vegetables and grapes, Family history of Cancer

NAS06024

Huang

1997

Citrus fruits, preserved, exposed at age of 10, cases / control were from Guangdong province

Yes vs No

Question-naire


104 104 2 2.169 No 1.12-4.21


2.2.2.2 Other fruits Non-preserved fruits: Adulthood consumption

1 June, 2006


46


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

Apple, 3 years ago



104 104 Contin-uous

0.64 N/A 0.46-0.9


NAS00825

Chen

1997

Banana, 3 years ago



104 104 Contin-uous

0.59 N/A 0.42-0.82


NAS00825

Chen

1997

Grape, 3 years ago



104 104 Contin-uous

0.42 N/A 0.28-0.64


NAS00825

Chen

1997

Water melon, 3 years ago



104 104 Contin-uous

1.56 N/A 1.07-2.27


NAS00825

Chen

1997

Peach, 3 years ago



104 104 Contin-uous

0.65 N/A 0.46-0.91


NAS00825

Chen

1997

grape, unknown age at consumption



104 104 Contin-uous

0.31 N/A 0.17-0.58

N/A <0.001 Age, Sex, Area of Residence, Consumption of Plum Vegetable/ Preserved Prune, No separate kitchen, Kitchen Range wo chimney, Family Cancer History

1 June, 2006


47

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

Grape Less than once / month to 1- 4 times / week




0.05-0.29

N/A <0.001 Age, Sex, Area of Residence, Plum Vegetable/ Preserved Plum, No separate kitchen, Kitchen Range wo Chimney

NAS06024

Huang

1997

Apple, exposed 3 years before disease diagnosed, cases and control were from Guangdong province



104 104 2 0.641 No 0.46-0.9


NAS06024

Huang

1997

Peach, exposed 3 years before disease diagnosed, cases and control were from Guangdong province



104 104 2 0.651 No 0.46-0.91


NAS06024

Huang

1997

Watemelon, exposed 3 years before disease diagnosed, cases and control were from Guangdong province



104 104 2 1.559 No 1.07-2.27


NAS06024

Huang

1997

Banana, exposed 3 years before disease diagnosed, cases and control were from Guangdong province



104 104 2 0.587 No 0.42-0.82


1 June, 2006


48

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Banana, exposed 3 years before disease diagnosed, cases and control were from Heilongjiang province



104 104 2 0.567 No 0.38-0.85


NAS06024

Huang

1997

Grape, cases and control were from Guangdong province



104 104 2 0.312 No 0.17-0.58

<0.001 N/A Age, Sex, Family history of Cancer, dried vegetables / oranges, No separate kitchen

Non-preserved fruits: Childhood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Baby Foods: Grapes

< 3 times / week to 3-7 times / week



72 72 2 0.66 N/A N/A Not significant


NAS00825

Chen

1997

Grape, 10 years old Logistic regression model



104 104 Contin-uous

0.63 N/A 0.4-0.99


NAS00825

Chen

1997

apple, 10 years old N/A FFQ - Study-specific




1 June, 2006


49

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

banana, 10 years old





NAS00825

Chen

1997

water melon, 10 years old





NAS00825

Chen

1997

peach, 10 years old N/A FFQ - Study-specific




NAS01459

Yu

1989

other fresh fruits (not oranges/ tangerines), ages 1-2

Rarely to weekly



110 139 3 0.6 Rarely 0.3-1.2



NAS01459

Yu

1989

other fresh fruits (not oranges/ tangerines), at age 10

Rarely to daily



110 139 4 0.3 Rarely 0.1-1.1



NAS01520

Yu

1988

other fresh fruits (not oranges / tangerines) ages 1 to 2




N/A Age, sex

NAS01520

Yu

1988

other fresh fruits (not oranges/ tangerines at age 10




N/A Age, sex

NAS06024

Huang

1997

Banana, exposed at age of 10, cases and control were from Heilongjiang province



104 104 2 0.472 No 0.29-0.77


1 June, 2006


50

Preserved plums: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Dried plum (chan pai mui)




N/A N/A

NAS00577

Yuan

2000

preserved plum (gar ink gee)




N/A N/A

NAS00825

Chen

1997

preserved prune, 3 years ago





NAS00825

Chen

1997

preserved plum, 3 years ago





NAS00825

Chen

1997

Preserved prune N/A FFQ - Study-specific


104 104 Contin-uous

2.59 N/A 1.04-8.41

N/A 0.043 Age, Sex, Area of Residence, Consumption of Plum Veg/ grape, No separate kitchen, Kitchen Range wo chimney, Family Cancer History

NAS00825

Chen

1997

Preserved Plum Less than once per month to 1-4 times per month




0.72-3.9

N/A <0.05 Age, Sex, Area of Residence, Plum Vegetable/ Grape, No separate kitchen, Kitchen Range wo Chimney

1 June, 2006


51

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

chan pai mui, preserved (salted) plum, 3 years prior to diagnosis



110 139 N/A N/A N/A N/A N/A Not significant

N/A

NAS01459

Yu

1989

gar ink gee preserved (salted plum),, 3 years prior to diagnosis




N/A

NAS01459

Yu

1989

chan pai mui, preserved (salted plum), unsure time of consumption



110 139 N/A N/A N/A N/A N/A Signif- icant

Age, sex, area of residence, salted fish, fermented fish sauce, moldy bean curd, salted shrimp paste, gar ink gee, tomatoes

NAS01459

Yu

1989

gar ink gee, preserved (salted plum), unsure time of consumption




Age, sex, area of residence, salted fish, fermented fish sauce, moldy bean curd, chan pai mui, salted shrimp paste, tomatoes

NAS01608

Yu

1986

dried fruits (chan pai mui, gar ink gee), at 10 years of age or 3 years prior to diagnosis


China, Hong Kong




Preserved plums: Childhood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


52

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

preserved prune, 10 years old



104 104 Contin-uous

2.17 N/A 1.12-4.21


NAS00825

Chen

1997

preserved plum, 10 years old



104 104 Contin-uous

2.10 N/A 1.12-3.91


NAS01459

Yu

1989

preserved (salted) plum, at age 10

Rarely to daily



110 139 4 N/A Rarely N/A N/A 0.01 Age, sex, area of residence, consumption of salted fish during weaning

NAS01459

Yu

1989

gar ink gee, preserved (salted) plum, at age 10

Rarely to daily




NAS01520

Yu

1988

various dried plums, at age 10




N/A Age, sex

NAS01608

Yu

1986

chan pai mui, gar ink gee, at 10 years of age or 3 years prior to diagnosis


China, Hong Kong




NAS06024

Huang

1997

Preserved plums, exposed at age of 10, cases and control were from Guangdong province

Yes vs No

Question-naire


104 104 2 2.095 No 1.12-3.91


Preserved olives: Adulthood consumption Case-control (3)

1 June, 2006


53

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Olives in Brine




72 72 2 2.0 N/A 1.36-3.72


NAS00424

Laouamri

2001

Seasonings: Dried Olives




72 72 2 4.66 N/A 1.51-14.33


NAS01056

Lee

1994

salted black olives, during adulthood

Never to more than once a month


Singa-pore


200 406 3 1.6 Never 0.3-7.5


NAS01381

Jeannel

1990

During Preceding Year to Diagnosis: Pickled Olives

Less than once a month to > 8 times / month




N/A N/A N/A Age, sex, area of residence, living condition score

NAS01381

Jeannel

1990

Preceding Year to Diagnosis: Pickled Olives

<once/ month to > 8 times / month




N/A N/A N/A Age, sex, area of residence

Preserved olives: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

salted black olives, at age 10



Singa-pore


151 344 3 0.3 Never 0.1-0.9


1 June, 2006


54

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

salted olive, at age 10




N/A Age, sex

Other preserved fruits: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Raisins




72 72 2 0.2 N/A 0.08-0.17


NAS00577

Yuan

2000

dried red date (gone hong zhao)




N/A N/A

NAS01608

Yu

1986

dried red date, at 10 years of age or 3 years prior to diagnosis


China, Hong Kong




Other preserved fruits: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

dried red date, at age 10




N/A Age, sex

1 June, 2006


55

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01608

Yu

1986



China, Hong Kong




2.3 Pulses (legumes) Non-preserved pulses/legumes Cohort (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

RR Ref group

CI P value

p value for trend

Adjusted for

NAS06046

Lin

1997

Non-fermented pulses

<2 times a week 6+ times a week

Question-naire

China, Taiwan

Chinese 9775 Min 30/ Males

N/A N/A 3 7.2 <2 times a week

1.4-37.5

<.001 N/A Age, EBV status, family history of NPC, nasopharyngitis


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Baby foods: Lentils

< 3 times a week to 3-7 times a week



72 72 2 2.25 N/A 1.0-5.0


NAS00531

Ward

2000

Adult Dietary Intake: consumption of fresh soybean products

Never vs. ever


China, Taiwan


375 327 2 N/A No N/A Not signif-icant

N/A Age, sex, ethnicity/ race, total calories, mothers questionnaire

1 June, 2006


56

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Age 10: Fresh soybean products

≤1.96

grams to ≥ 6.4 grams


China, Taiwan


93 114 4 0.4 ≤1.96 grams

0.2-1.0

N/A N/A Age, sex, ethnicity/ race, total calories, mothers questionnaire

NAS00531

Ward

2000


≤1,6 grams to > 4 grams


China, Taiwan


90 110 4 0.7 ≤1,6 grams

0.3-1.7


NAS00531

Ward

2000

During Weaning: Fresh soybean products

None to > 0 grams


China, Taiwan


84 104 2 1.1 None 0.5-1.2


NAS00531

Ward

2000

Mother's diet during breastfeeding: fresh soy products

Lowest to highest


China, Taiwan


375 327 3 0.7 Lowest 0.3-1.6

N/A N/A Age, sex, ethnicity/ race, Vegetable intake

NAS00531

Ward

2000


Lowest to highest


China, Taiwan


375 327 3 0.6 Lowest 0.2-1.5

N/A N/A N/A

Preserved soy/tofu: Adulthood consumption Case-control (8) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: fermented soybean products

Never vs. ever


China, Taiwan




1 June, 2006


57

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Fermented beans/ pastes (not specified, but measured fermented bean curd (fu yu), fermented bean paste (tau ban cheung)

Less than monthly to weekly or more




1.39-2.22

N/A <0.001 Sex, Age, Educational Level, Smoking, Exposure to smoke from heated rapeseed oil and burning coal while cooking, Occupational exposure to chemical fumes, History of chronic ear and nose condition

NAS01056

Lee

1994

salted soy beans, during adulthood

Never exposed to > 3 times per week



199 406 5 6.7 Never 1.2-36.6


NAS01190

Zheng

1993

Salted Soya Bean Pastes


China Chinese 410 N/A. Mixed


N/A N/A

NAS01459

Yu

1989

moldy bean curd, 3 years prior to diagnosis





NAS01459

Yu

1989

moldy bean curd, unsure time of consumption




N/A Age, sex, area of residence, salted fish, fermented fish sauce, salted shrimp paste, chan pai mui, gar ink gee, tomatoes

NAS01608

Yu

1986

moldy bean curd, at 10 years or 3 years prior to diagnosis





1 June, 2006


58

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

moldy bean curd, preserved, 3 years prior to diagnosis





NAS01922

Ning

1990

smelly bean curd, consumption 3 years prior to diagnosis





NAS01922

Ning

1990

fermented soy/flour paste, consumption 3 years prior to diagnosis





NAS06023

Zou

1999

Fermented soy < 9 times a month to ≥ 9 times a month



100 202 2 1.45 < 9 times a month

0.78-2.83

N/A N/A Age, Sex, Live in area with high level of background radiation, Alcohol, Smoking habits, Salted fish

NAS06023

Zou

1999

tofu, soy products

Never to ≥ 9 times a month



102 201 2 2.36 Never 0.26-21.3

0.17 N/A Unadjusted

Preserved soy/tofu: Childhood consumption Case-control (6) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

2.3 Fermented soybean products, at Age 10

< 16 grams to ≥ 118.8 grams


China, Taiwan


98 115 4 0.5 < 16 grams

0.2-1.2


1 June, 2006


59

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Fermented soybean products, at Age 3

None to ≥80.4 grams


China, Taiwan


93 111 4 0.7 None 0.3-1.9


NAS00531

Ward

2000

During Weaning Fermented soybean products

None to 12.04 grams


China, Taiwan


90 113 4 0.6 None 0.3-1.3


NAS01056

Lee

1994

salted soy beans, at age 10 year

Never exposed to 1-3 times a week



146 342 4 1.1 Never 0.5-2.2


NAS01056

Lee

1994

fermented bean curd, at age 10




151 341 4 0.8 Never 0.4-1.8


NAS01459

Yu

1989

Moldy bean curd, ages 1-2

Rarely to weekly



110 139 3 N/A Rarely N/A N/A 0.05 Age, sex, area of residence, salted fish consumption during weaning

NAS01459

Yu

1989

Moldy bean curd, at age 10

Rarely to daily




NAS01520

Yu

1988

fermented soy bean paste, ages 1 to 2

Rarely to weekly



128 174 3 3.6 Rarely 1.6-8.1

N/A 0.007 Age, sex

NAS01520

Yu

1988

fermented soy bean paste, at age 10

Rarely to weekly



128 174 3 1.5 Rarely 0.8-3.0

N/A Not signif-icant

Age, sex

1 June, 2006


60

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01520

Yu

1988

moldy bean curd, consumed at age 10



128 174 N/A N/A N?A N/A Not signif-icant

N/A Age, sex

NAS01520

Yu

1988

fermented soy bean paste, consumed by subject at age 1-2

Rarely to monthly



128 174 Contin-uous

r2 = -.23

Rarely N/A 0.240 N/A Age, sex, salted fish during pregnancy, salted duck egg / salted mustard green / chung choi during weaning, dried fish during ages 1 and 2 yr

NAS01520

Yu

1988


Rarely to weekly



128 174 Contin-uous

r2 = .988


NAS01608

Yu

1986






NAS01922

Ning

1990

moldy bean curd, preserved, at age 10





NAS01922

Ning

1990

smelly bean curd, consumption at 10 years of age





1 June, 2006


61

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

fermented soy/flour paste, consumption at 10 years of age





Other preserved pulses/legumes Cohort (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

RR Ref group

CI P value

p value for trend

Adjusted for

NAS06046

Lin

1997

Fermented pulses

<2 times a week v. 6+ times a week

Question-naire

China, Taiwan



2.2-72.3



Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

salted black beans, consumption during adulthood

Never exposed to > 3 times per month



200 406 4 2.1 Never 0.8-5.4


NAS01056

Lee

1994

salted black beans, consumption at age 10 years

Never exposed to more than three times per month



148 341 4 1.0 Never 0.4-2.3


1 June, 2006


62

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01520

Yu

1988

fermented black bean paste, consumed by subject between ages 1 to 2 years

Rarely to weekly



128 174 3 4.6 Rarely 1.8-11.4

N/A 0.0009 Age, sex

NAS01520

Yu

1988

fermented black bean paste, consumed by subject at age 10

Rarely to weekly



128 174 3 1.4 Rarely 0.6-3.1


Age, sex

NAS06023

Zou

1999

Fermented beans <9 times/ month to ≥9 times/ month



97 192 2 2.1 <9 times per month

1.3-3.4

0.004 N/A Age, sex, year of death

2.4 Nuts and seeds Nuts and seeds: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Nuts and Seeds



72 72 2 0.33 N/A N/A <0.05 N/A Age, sex, area of residence

NAS00577

Yuan

2000

dried ginko seed (bei guo)




N/A N/A

NAS01812

Geser

1978

Fennel in households of cases and controls


China, Hong Kong

Chinese 300 N/A/ Mixed

143 141 2 0.17 No 0.05-0.59

N/A N/A Age, Sex

1 June, 2006


63

Study identifier

Author, Yr


Assess-ment

Tool




No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01812

Geser

1978

Xanthozylon Seeds


China, Hong Kong


150 150 N/A N/A N/A N/A N/A N/A Sex, Age, Vinegar, Flavor Essence, Mustard Paste, Chinese Wine, Bread, Oyster soy, Use of ancestral alters and Buddhist alters

Nuts and seeds: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool




No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01113

Zheng

1994

Melon seeds, between the ages of 2 and 10

Yes vs No



88 174 2 2.8 No N/A 0.02 N/A Age, sex, area of residence, Sociodemographic score (housing in childhood, presence of windows, monthly income the year before diagnosis)

NAS01520

Yu

1988

dried gingko seed, consumed by subject at age 10




N/A Age, sex

2.5.1 Meat Preserved meat: Adulthood consumption Case-control (7) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


64

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Dried, salted meat

Currently to twenty years ago



72 72 2 4.75 N/A 1.8-12.5

0.01 N/A Age, sex, area of residence

NAS00531

Ward

2000

Adult Dietary Intake: cured meats

Never vs. Ever


China, Taiwan


375 327 2 N/A Never N/A Not signif-icant

N/A Age, sex, ethnicity/ race

NAS00531

Ward

2000

Adult Dietary Intake: smoked meats

Never vs. Ever


China, Taiwan




NAS00544

Chelleng

2000

smoked meat Never & rarely to frequently

Unknown-NA

India Indian 141 Mean 44/ Mixed

47 94 2 10.8 Never & rarely

3.4-39

0.0002 N/A Age, sex, ethnicity/ race, Area of residence, Alcohol / Smoking / betel nut chewing habits, type of house, number of windows, kitchen inside/ outside, soot in living room, type of cooking fuel, smokeless tobacco use

NAS00577

Yuan

2000

Preserved Meats (not specified: ham, cured duck, salted pork)





1.12-2.79

N/A 0.56 Age, sex, area of residence, environ-mental factors, smoking, chemical fumes, history of ear/nose condition

1 June, 2006


65

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

rou gan, dried sweetened meat, during adulthood




N/A Age, sex, ethnicity/ race, education, belachan, mei chye, canned, salted, & pickled vegetables, vitamin C, salted soy beans, sze chuan chye, kiam chye, vitamin E

NAS01113

Zheng

1994

Salted dried and tinned meat




N/A N/A

NAS01922

Ning

1990

cured meat, 3 years prior to diagnosis




N/A N/A

NAS01922

Ning

1990

smoked meat, consumption 3 years prior to diagnosis




N/A N/A

NAS01922

Ning

1990

salted meat, 3 years prior to diagnosis




N/A N/A

Preserved meat: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


66

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Cured Meat, At Age 10

Yes vs. no Dietary History question-naire

China, Taiwan


89 111 2 1.11 No 0.6-2


NAS00531

Ward

2000



China, Taiwan


92 109 2 0.8 No 0.4-1.8


NAS00531

Ward

2000

Smoked meat, Age 10


China, Taiwan


92 114 2 1.1 No 0.5-2.4


NAS00531

Ward

2000

Smoked meat, at Age 3


China, Taiwan


92 110 2 1.2 No 0.4-3.3


NAS00531

Ward

2000

Smoked meat, During Weaning


China, Taiwan


89 112 2 2.2 No 0.2-27.6


NAS01056

Lee

1994

rou gan, dried sweetened meat, usually pork, at 10 years old

Never to >1 times per week



149 342 3 0.8 Never 0.2-3.0

N/A 0.08 Age, sex, ethnicity/ race, education

NAS01381

Jeannel

1990

Intake Before Weaning: Quaddid (spiced dried meat stored in oil)

Yes vs. No FFQ - Study-specific


80 160 2 3.2 No N/A 0.2 N/A Age, sex, area of residence, lifestyle factors

NAS01381

Jeannel

1990

Intake During Weaning: Quaddid (spiced dried meat stored in oil)

<1 time a month to 2+ times a week



80 160 3 2.8 <1 time a month

N/A N/A N/A Age, sex, area of residence, lifestyle factors

1 June, 2006


67

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

cured meat, at age 10




N/A N/A

NAS01922

Ning

1990

smoked meat, at age 10




N/A N/A

NAS01922

Ning

1990

salted meat, at age 10




N/A N/A

NAS01922

Ning

1990





N/A N/A

2.5.1.1 Fresh Meat Fresh meat: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00577

Yuan

2000

Organ meat, fresh




N/A Unadusted

NAS00749

Armstrong

1998

Fresh pork/beef liver, at age 10 and age 5 years prior to diagnosis





NA 0.0001 N/A Unadjusted

1 June, 2006


68

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

other fresh pork/beef organs, 5 years prior to diagnosis





1.89-11.3

N/A .009 Unadjusted

NAS01459

Yu

1989

Fresh meat, 3 years prior to diagnosis





NAS01922

Ning

1990

fresh liver, 3 years prior to diagnosis





Fresh meat: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

fresh pork/beef liver, at age 10 and age 5 years prior to diagnosis






NAS00749

Armstrong

1998

other fresh pork/beef organs, at age 10





0.51-2.46

N/A N/A Unadjusted

NAS01459

Yu

1989

Fresh meat, at age 10





1 June, 2006


69

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01459

Yu

1989

Fresh meat, at age 1-2





NAS01520

Yu

1988

fresh meats, during weaning




NAS01520

Yu

1988

fresh meats, ages 1-2




NAS01520

Yu

1988

fresh meats, at age 10




N/A Age, sex

NAS01922

Ning

1990

fresh liver, at 10 years of age





2.5.1.2 Processed meat Processed meat: Adulthood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


70

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00700

Farrow

1998

Processed, preserved meat (ham, bacon, sausage, liverwurst, hot dogs)

Lowest to highest

FFQ – Block

United States


129 204 4 1.54 Lowest 0.71-3.33


NAS01056

Lee

1994

lapcheong, Chinese sausage, during adulthood

Never to 3+ times a month


Singa-pore


200 406 4 1.0 Never 0.3-2.8


NAS01153

West

1993

Processed meat, including ham and longanisa

Low to high tertile

Unknown Philip-pines

Filipino 205 11-83/ Mixed

104 205 3 0.46 Low tertile

0.2-1.0

N/A N/A Age, sex, fresh fish, processed meat, hospital ward, Smoking, Burning anti-mosquito coils. Dust/ exhaust, Formaldehyde, Herbal medicines, Education

NAS01608

Yu

1986

liver sausage, at 10 years of age or 3 years prior to diagnosis





NAS06023

Zou

1999

Smoked, processed meat

Yes vs. no Question-naire


102 202 2 1.8 No 1.09-2.97

0.02 N/A Unadjusted

Processed meat: Childhood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

1 June, 2006


71

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

lapcheong, Chinese sausage, at age 10



Singa-pore


149 344 4 0.8 Never 0.3-2.4


NAS01520

Yu

1988

liver sausage, consumed by subject at age 10




N/A Age, sex

NAS01608

Yu

1986






Processed pork Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01520

Yu

1988

Ham, at age 10




N/A Age, sex

NAS01520

Yu

1988

Pork sausage, at age 10




N/A Age, sex

NAS01608

Yu

1986

Pork sausage, at age 10 or adult





2.5.1.3.1 Beef

1 June, 2006


72


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01113

Zheng

1994

Beef <2 times per year to 1+ times per week



88 175 3 0.6 <2 times per year

N/A 0.30 N/A Age, sex, SES, area of residence

NAS04944

Armstrong

1978

Beef Yes or no Recall Malaysia Chinese 210 25-81/ Mixed

60 150 2 0.4 no N/A <.05 N/A Age, sex, SES, ethnicity/ race, area of residence, lifestyle factors


Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

r2 Ref group

CI P value

p value for trend

Adjusted for

NAS00817

Koo

1997

Beef N/A Per capita consumption

China, Hong Kong

Chinese N/A N/A/ Male N/A N/A Correlation/ regression

r2 = -0.87

N/A N/A .026 N/A Age

NAS00817

Koo

1997

Beef N/A Per capita consumption

China, Hong Kong

Chinese N/A N/A/ Female

N/A N/A Correlation/ regression

r2 = -0.84

N/A N/A .034 N/A Age

2.5.1.3.2 Pork Non-processed pork Ecological (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

r2 Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


73

Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

r2 Ref group

CI P value

p value for trend

Adjusted for

NAS00817

Koo

1997

Pork N/A Per capita consumption

China, Hong Kong


r2 = -0.92

N/A N/A 0.01 N/A Age

NAS00817

Koo

1997

Pork N/A Per capita consumption

China, Hong Kong



r2 = -0.83



Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01190

Zheng

1993

Salted pork N/A FFQ - Study-specific

China Chinese 410 N/A./ Mixed


N/A Un-adjusted

NAS01520

Yu

1988

Ham, at age 10




N/A Age, sex

NAS01520

Yu

1988





N/A Age, sex

NAS01520

Yu

1988

Salted pork, at age 10




N/A Age, sex

1 June, 2006


74

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01608

Yu

1986

Salted pork, at age 10 or adult





NAS01608

Yu

1986






2.5.1.3.4 Organ meats Non-processed organ meats: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Organ meat, fresh




N/A Unadusted

NAS00749

Armstrong

1998

Fresh pork/beef liver, 5 years pre-diagnosis





1.83-6.84

N/A .001 Unadjusted

NAS00749

Armstrong

1998






1.89-11.3

N/A .009 Unadjusted

1 June, 2006


75

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

fresh, pork/beef liver, trichotomous categories: includes dietary information at age 10 and age 5 years prior to diagnosis





N/A N/A .0001 SES, salted fish, recent consumption, salted egg/ shrimp / chinese flowering cabbage/ oranges/ tangerines, lifetime consumption, beer consumption

NAS01459

Yu

1989

liver, 3 years prior to diagnosis





NAS01922

Ning

1990






Non-processed organ meats: Childhood consumption Case-control (4) Study identifier

Author,Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Fresh pork/beef liver, at age 10





0.97-4.05

N/A N/A Unadjusted

NAS00749

Armstrong

1998






0.51-2.46

N/A N/A Unadjusted

1 June, 2006


76

Study identifier

Author,Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

liver, at age 10





NAS01459

Yu

1989

liver, at age 1-2





NAS01520

Yu

1988

liver, consumed by subject at age 10




N/A Age, sex

NAS01520

Yu

1988

liver, consumed by subject ages 1-2




N/A Age, sex

NAS01922

Ning

1990






Processed organ meats Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988





N/A Age, sex

1 June, 2006


77

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS01608

Yu

1986






2.5.1.4 Poultry Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Baby foods: chicken

<3 times a week to 3-7 times a week



35 47 2 0.2 <3 times a week

0.06-0.6


NAS01381

Jeannel

1990

Chicken, during childhood




80 160 4 4.7 <1 time a month



Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

r2 Ref group

CI P value

p value for trend

Adjusted for

NAS00817

Koo

1997

Poultry N/A Per capita consumption

China, Hong Kong


r2 = -0.83


NAS00817

Koo

1997

Poultry N/A Per capita consumption

China, Hong Kong



r2 = -0.84


1 June, 2006


78

2.5.2 Fish Non-preserved fish Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01459

Yu

1989

Fresh fish sauce, adult





NAS01459

Yu

1989

Fresh fish sauce, age 10





NAS01459

Yu

1989

Fresh fish sauce, age 1-2





NAS01520

Yu

1988

Fresh fish, age 10




N/A Age, sex

NAS01520

Yu

1988

Fresh fish, age 1-2




NAS01520

Yu

1988

Fresh fish, during weaning



128 174 N/A N/A N/A N/A 0.09 N/A Sex

NAS01922

Ning

1990

boiled fish, fresh, at age 10





1 June, 2006


79

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

boiled fish, fresh, 3 years prior to diagnosis






Author, Yr

Exposure Expo-sure range

Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

Regression Slope

Ref group

CI P value

p value for trend

Adjusted for

NAS00817

Koo

1997

Saltwater Fish


China, Hong Kong

Chinese N/A N/A/ Male N/A N/A N/A r2 = -0.83 N/A N/A 0.039 N/A Age

NAS00817

Koo

1997

Saltwater Fish


China, Hong Kong


N/A N/A N/A r2 = -0.84 N/A N/A 0.038 N/A Age

NAS00817

Koo

1997

Freshwater fish


China, Hong Kong

Chinese N/A N/A/ Male N/A N/A N/A r2 = -0.70 N/A N/A 0.124 N/A Age

NAS00817

Koo

1997

Freshwater fish


China, Hong Kong


N/A N/A N/A r2 = -0.77 N/A N/A 0.070 N/A Age

2.5.2.1 Salted Fish Salted fish: Adulthood consumption Cohort (1)

1 June, 2006


80

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Chi-square

Ref group

CI P value

p value for trend

Adjusted for

NAS06011

Zou

1994

Salted fish, 1960s

none to 1+ times a week



N/A N/A 2 Chi-square = 12.91

Not exposed

N/A <.001 N/A Unadjusted

NAS06011

Zou

1994

Salted fish, 1970s





Not exposed


NAS06011

Zou

1994

Salted fish, 1980s





Not exposed

N/A .214 N/A Unadjusted

Case-control (21) Meta-analysis Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group CI P value p value for trend

Adjusted for

NAS00531

Ward

2000

Salted fish, adult intake

5g/wk Dietary History question-naire

China, Taiwan


375 327 2 0.8 No 0.5-1.2

Not signif-icant


NAS00577

Yuan

2000

Salted fish Less than monthly to weekly or more




0.86-3.88

N/A 0.07 Age, sex, area of residence, env factors, smoking, chemical fumes, history of ear/nose condition

1 June, 2006


81

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS00749

Armstrong

1998

Salted fish, 5 years prior





2.23-7.99

Signif-icant

.001 Unadjusted

NAS01056

Lee

1994

Salted fish, adult

Never to 3+ times a week



200 406 4 4.4 Never 0.7-25.9

Not signif-icant

0.6 Age, sex, ethnicity/ race, education

NAS01113

Zheng

1994

Salted fish, year before dx




N/A Age, sex, area of residence, SES

NAS01141

Zheng

1994

Salted fish, tough meat

Never and yearly to weekly and daily



205 205 3 11.2 Never and yearly

4.6-32.0

Signif-icant


NAS01141

Zheng

1994

Salted fish, soft meat





4.1-152

Signif-icant


NAS01153

West

1993

Salted fish Low to high tertile

Unknown Philippines Filipino 205 11-83/ Mixed

104 101 3 1.3 Low tertile 0.69-2.6

Not signif-icant

N/A Age, sex, fresh fish, processed meat, hospital ward

NAS01190

Zheng

1993

Highest consumption of salted fish from 3 time periods: last 7 years, at age 10, and in the first 3 years




N/A N/A

1 June, 2006


82

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS01248

Sriamporn

1992

Salted fish Freshwater only, sea salted +/- once a week


Thailand Thai 240 Mean 47/ Mixed

120 120 3 2.5 Fresh-water only

1.2-5.2

Signif-icant

N/A Age, sex, area of residence, smoking, alcohol, occupation

NAS01459

Yu

1989

Salted fish, 3 years prior to dx

Rarely to daily



306 306 4 1.8 Rarely 0.9-3.6

Not signif-icant

<.05 Age, sex, area of residence

NAS01608

Yu

1986

Salted fish, adult

Rarely to daily


China, Hong Kong


250 250 4 7.5 Rarely 0.9-65.3

Not signif-icant

N/A Age, sex

NAS01608

Yu

1986

Salted fish head soup, adult

Rarely to more than once a month


China, Hong Kong


250 250 2 4.2 Rarely 1.6-11.7

Signif-icant

N/A Age, sex

NAS01922

Ning

1990

salted fish, ever consumed

Ever vs. Never



100 300 2 2.2 Never 1.3-3.7


NAS01922

Ning

1990

Salted fish age at first exposure

Never exposed to older than 21



100 300 4 1.5 Never 0.7-3.3

N/A 0.0006 Age, Sex, Area of residence

NAS01922

Ning

1990

salted fish, duration of consumption (years)

Never exposed to more than 21 years



100 300 4 2.8 Never 1.4-5.6


NAS01922

Ning

1990

2.5.2 salted fish, 3 years prior to diagnosis

Never to weekly or daily




0.41 Age, Sex, Area of residence

1 June, 2006


83

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS01922

Ning

1990

salted fish, age/ duration at first exposure

Never exposed to age 21+/ duration 11+ years



100 300 7 2.5 N/A N/A N/A N/A Age, Sex, Area of residence

NAS01922

Ning

1990

salted fish, age/ duration at first exposure (those who consumed at least monthly during the earliest decade of exposure)

Never exposed to 11+ years at first exposure and 11+ years duration




NAS02182

Armstrong

1983

Salted fish, current consumption as adults

N/A N/A Malaysia Chinese 200 N/A/

Mixed


N/A Age, Sex, Area of residence, Ethnicity/ Race

NAS04928

Henderson

1976

Current use of salted fish

N/A N/A United States

Chinese 423 Mean 52/ Mixed


N/A Age, Sex, Area of residence, SES

NAS05679

Yang

2005

Salted fish, moldy and firm, after age 10


Taiwan Chinese 2444 Mean 47/ Mixed


N/A Age, Sex, Family history of NPC

NAS06003

Ye

1995

salted fish ≤ 4 time per month to > 4 times per month



135 135 2 5.0 ≤ 4 time per month

1.26- 19.6


1 June, 2006


84

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS60010

Cai

1996

Salted Fish <12 times per month to ≥12 times per month



115 115 2 1.318 < 12 times per month

0.995-1.793


NAS06021

Chen

1994

Salted Fish frequently consumed

Question-naire


28 28 Contin-uous

r2= 0.8661

N/A N/A 0.008 N/A Sex, Age

NAS06021

Chen

1994

Salted Fish, frequently consumed

Yes or No Question-naire


28 28 2 5.51 No 1.74-17.46

<0.01 N/A Sex, Age

NAS06022

Wang

1993

Salted Fish, consumed frequently

less consumed to frequently consumed

Question-naire


122 122 2 8.99 less consumed

N/A 0.0127 N/A Consumption of pork fat, colored vegetables, whole grains, plant oils, and vegetables, Non-nutrient chemicals, smoking in living area, Sex, Age, SES

NAS06023

Zou

1999

Salted Fish < 9 times a month to ≥ 9 times a month

Question-naire


100 202 2 2.8 < 9 times a month

1.52-5.18

Significant N/A Age, Sex, Live in area with high level of background radiation, Alcohol, Smoking habits, Consumption of fermented soy

1 June, 2006


85

Salted fish: Childhood consumption (Age 10) Cohort (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Chi-square

Ref group

CI P value

p value for trend

Adjusted for

NAS06011

Zou

1994

Salted fish, childhood





Not exposed



Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS00531

Ward

2000

Salted fish, at age 10

Yes or no Dietary History question-naire

China, Taiwan


82 110 2 1.5 No 0.8-2.8

Not signif-icant


NAS00749

Armstrong

1998






1.59-4.75

Signif-icant

N/A Unadjusted

NAS00821

Hildesheim

1997

Salted fish during childhood

Yes or no Unknown China, Taiwan

Chinese 684 15-74/ Mixed

364 320 2 1.4 No 0.47-4.5

Not signif-icant

N/A Age, sex

NAS01056

Lee

1994





161 369 5 0.8 Never 0.2-2.9

Not signif-icant


NAS01113

Zheng

1994

Salted fish, steamed or fried, age 2-10

Rarely v. monthly/ weekly



88 176 2 1.4 Rarely N/A 0.2 N/A Age, sex, area of residence, SES

1 June, 2006


86

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01113

Zheng

1994

Salted fish soup, age 2-10





NAS01141

Zheng

1994

Salted fish, tough meat, age 10





5.1-16.4

Signif-icant


NAS01141

Zheng

1994

Salted fish, soft meat, age 10





5.2-20.7

Signif-icant


NAS01190

Zheng

1993





N/A N/A

NAS01459

Yu

1989


Rarely to daily



306 306 4 2.1 Rarely 1.2-3.6

Signif-icant


NAS01520

Yu

1988

Salted fish, age 10

Rarely to monthly



128 174 3 1.5 Rarely 0.5-4.3

Not signif-icant

N/A Age, sex

NAS01520

Yu

1988

Salted fish head soup, age 10




N/A Age, sex

NAS01608

Yu

1986

Salted fish, age 10

Rarely to more than weekly


China, Hong Kong


250 250 3 37.7 Rarely 14.1-100

Signif-icant

N/A Age, sex

1 June, 2006


87

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01608

Yu

1986




China, Hong Kong


250 250 2 5.1 Rarely 2.6-10.4

Signif-icant

N/A Age, sex

NAS01712

Armstrong

1983

Salted fish, child Ever v. never

Unknown Malaysia Chinese 200 Mean 43/ Mixed

100 100 2 17.4 Never 2.7-111

Signif-icant


NAS01766

Lanier

1980

Salted fish, child Yes or no Question-naire

United States, Alaska

Alaskan native

26 32-80/ Mixed

13 13 2 4.0 No 0.4-19.7

Not signif-icant

N/A Age, sex, area of residence, ethnicity/ race

NAS01922

Ning

1990

salted fish, at age 10 years




100 300 4 6.7 Never N/A N/A 0.003 Age, Sex, Area of residence, salted shrimp paste and carrot consumption at 10 years

NAS01922

Ning

1990

steamed salted fish, at age 10

Ever vs Never



100 300 2 4.2 Never 2.2-8.3


NAS01922

Ning

1990

fried, grilled, broiled salted fish, at age 10

Ever vs Never



100 300 2 1.6 Never 0.8-3.2


NAS02182

Armstrong

1983

NPC and Salted Fish, during childhood

Ever vs Never

N/A Malaysia Chinese 200 N/A/

Mixed

100 100 2 3.0 Never N/A 0.04 N/A Age, Sex, Area of residence, Ethnicity/ Race

NAS02182

Armstrong

1983


Never to daily


Mixed

100 100 3 17.4 Never 2.7-111.1

N/A N/A Age, Sex, Area of residence, Ethnicity/ Race

1 June, 2006


88

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS02182

Armstrong

1983

NPC and Salted Fish, Consumption during adolescence



Mixed


1.2- 10.7


NAS05679

Yang

2005

Salted fish, moldy and firm, during childhood

Never vs. 1+ times/wk



502 1942 3 1.78 Never 0.82-3.89

Not signif-icant


NAS06020

Na

1988

Salted Fish, during childhood

N/A Question-naire


127 217 Contin-uous

r2= 1.575


N/A Area of residence, coal as family fuel, History of cancer/ naso-pharyngitis, Sex, Age

NAS06020

Na

1988


consume less to more

Question-naire


127 217 2 5.5 Consume less

1.16-35.89

<0.05 N/A Unadjusted

Salted fish: Childhood consumption (Ages 0-3) Case-control (10) Meta-analysis Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS00531

Ward

2000



China, Taiwan


86 102 2 1.0 No 0.5-2.1

Not signif-icant


NAS01056

Lee

1994

Salted fish, during infancy




200 406 3 1.2 Never 0.3-3.4

Not signif-icant

N/A Age, sex, ethnicity/ race, education

1 June, 2006


89

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01113

Zheng

1994

Salted fish, during weaning



87 171 2 2.4 No N/A 0.01 N/A Age, sex, area of residence, SES

NAS01113

Zheng

1994

Salted fish, steamed or fried, before 2





NAS01113

Zheng

1994

Salted fish soup, before 2





NAS01141

Zheng

1994

Salted fish, age 0-3





5.2-20.6

Signif-icant


NAS01190

Zheng

1993





N/A N/A

NAS01381

Jeannel

1990

Salted anchovies, during weaning




NAS01459

Yu

1989


Rarely to weekly



306 306 3 2.0 Rarely 1.1-3.6

Signif-icant


NAS01459

Yu

1989




306 306 2 2.1 No 1.2-3.6

Signif-icant


1 June, 2006


90

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01520

Yu

1988


Rarely to monthly



128 174 3 2.2 Rarely 0.7-7.6

Not signif-icant

.11 Age, sex

NAS01520

Yu

1988




128 174 2 2.6 No 1.2-5.6

.01 N/A Age, sex

NAS01608

Yu

1986

Salted fish, age 1-2 by mother

Never to often


China, Hong Kong


250 250 3 20.2 Never 6.8-60.2

Signif-icant

N/A Age, sex

NAS01608

Yu

1986

Salted fish, during weaning (mother)

Ever v. never


China, Hong Kong


250 250 3 7.5 Never 3.9-14.8

Signif-icant

N/A Age, sex

NAS01608

Yu

1986

Salted fish head soup, age 1-2 (mother)

Ever v. never


China, Hong Kong


250 250 2 8.3 Never 2.5-32.5

Signif-icant

N/A Age, sex

NAS01812

Geser

1978

Salted fish, after weaning


China, Hong Kong


150 150 2 2.6 No N/A < 0.01 N/A Unadjusted

NAS01812

Geser

1978

Salted Fish During Weaning

No salted fish / low traditional life-style index to yes salted fish/ high traditional lifestyle index


China, Hong Kong


98 89 6 2.2 No salted fish and low traditional life-style index


N/A traditional lifestyle: compilation of Chinese wine drinking, bread consumption, ancestral / Buddhist alters

1 June, 2006


91

Salted fish: Mother’s consumption during pregnancy or breastfeeding Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

Salted fish, during breast-feeding




49 96 3 2.0 never 0.3-10.6

Not signif-icant


NAS01056

Lee

1994

Salted fish, during pregnancy




46 94 3 1.3 never 0.4-3.7

Not signif-icant


NAS01459

Yu

1989

Salted fish, during nursing

Rarely to daily



306 306 4 2.3 Rarely 1.1-4.6

Signif-icant


NAS01459

Yu

1989


Rarely to daily



306 306 4 2.2 Rarely 1.1-4.6

Signif-icant


NAS01520

Yu

1988

Salted fish, while nursing

Rarely to monthly



128 174 3 4.9 Rarely 1.5-15.9

Signif-icant

.01 Age, sex

NAS01520

Yu

1988


Rarely to monthly



128 174 3 3.1 Rarely 1.1-8.8

Signif-icant

.003 Age, sex

2.5.2.2 Other preserved fish (excluding salted fish) Cohort (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

Chi-square

Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


92

Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

Chi-square

Ref group

CI P value

p value for trend

Adjusted for

NAS06011

Zou

1994

Salted and dried fish, 1960s





Not exposed


NAS06011

Zou

1994






Not exposed


NAS06011

Zou

1994






Not exposed



Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

Dried, unsalted fish, adult




195 405 3 2.2 Never 0.8-5.4

Not signif-icant


NAS01056

Lee

1994

Dried, unsalted fish, at age 10




141 337 3 0.1 Never 0.01-1.0

Signif-icant


NAS01056

Lee

1994

Dried, tiny fish, at age 10




148 345 5 0.6 never 0.02-2.1

Not signif-icant


NAS01056

Lee

1994

Dried, tiny fish, adult




190 306 5 1.1 never 0.3-3.8

Not signif-icant


1 June, 2006


93

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

Dried, tiny fish, infancy




59 96 4 0.7 never 0.05-8.6

Not signif-icant


NAS01056

Lee

1994

Dried, tiny fish soup, during infancy




60 96 4 4.2 never 0.4-42.8

Not signif-icant


NAS01056

Lee

1994

Preserved cuttlefish, adult




198 305 4 1.3 Never 0.5-2.9

Not signif-icant


NAS01056

Lee

1994

Preserved cuttlefish, at age 10




146 341 4 0.6 Never 0.1-1.8

Not signif-icant


NAS01056

Lee

1994

Preserved fish tidbits, adult




198 406 4 2.6 Never 0.6-10.0

Not signif-icant


NAS01056

Lee

1994

Preserved fish tidbits, at age 10




144 343 4 0.4 Never 0.1-1.3

Not signif-icant


NAS01056

Lee

1994

Fish gravy, adult Never to 3+ times a week



197 398 5 1.3 Never 0.6-2.7

Not signif-icant


NAS01056

Lee

1994

Fish gravy, at age 10




143 334 5 1.0 Never 0.4-2.4

Not signif-icant


1 June, 2006


94

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01459

Yu

1989

Fermented fish sauce -adult





NAS01459

Yu

1989

Fermented fish sauce -age 10

Rarely to daily



306 306 4 N/A Rarely N/A N/A .93 Age, sex, area of residence, salted fish

NAS01459

Yu

1989

Fermented fish sauce -age 1-2

Rarely to weekly




NAS01520

Yu

1988

Dried fish, age 10

Rarely to monthly



128 174 3 6.4 Rarely 1.6-26.8

Signif-icant

.04 Age, sex

NAS01520

Yu

1988

Dried fish, age 1-2

Rarely to monthly



128 174 3 2.2 Rarely 0.9-5.3

Not signif-icant

.002 Age, sex

NAS01520

Yu

1988

Fermented fish paste, age 10




N/A Age, sex

NAS01922

Ning

1990

dried anchovy, at age 10





NAS01922

Ning

1990

dried anchovy, 3 years prior to diagnosis





1 June, 2006


95

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS04944

Armstrong

1978

dried fish, for breakfast among families of cases/ controls


60 150 N/A N/A N/A N/A Signig-icant

N/A Unadjusted

NAS04944

Armstrong

1978

dried fish in three main daily meals combined, among cases and controls

Unclear Recall Malaysia Chinese 210 25-81/ Mixed


N/A Age, Sex, Area of residence, Ethnicity/ Race, Socio-economic status, Lifestyle Factors

2.5.3 Shellfish and other seafood Non-preserved seafood Case-control (4) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Seafood, fresh N/A FFQ - Study-specific



N/A N/A

NAS00749

Armstrong

1998

shrimp, 5 years pre-diagnosis




282 282 3 0.87 Monthly 0.47-1.62


NAS00749

Armstrong

1998

shrimp, at age 10 Monthly to more than weekly



282 282 3 0.57 Monthly 0.34-0.96

N/A N/A Unadjusted

1 June, 2006


96

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

shrimp, lifetime consumption, analysis includes dietary information at age 10 and age 5 years prior to diagnosis

Less than monthly to monthly and more




N/A 0.082 N/A SES, salted fish/pork/ beef liver, recent consumption, salted egg/ chinese flowering cabbage/ oranges/ tangerines/ beer lifetime consumption

NAS01922

Ning

1990

crab, fresh, at age 10




N/A N/A

NAS01922

Ning

1990

crab, fresh, 3 years prior to diagnosis




N/A N/A

NAS01922

Ning

1990

jellyfish, fresh, at age 10




N/A N/A

NAS01922

Ning

1990

jellyfish, fresh, 3 years prior to diagnosis




N/A N/A

NAS04944

Armstrong

1978

fresh prawns, at evening meal among families of cases / controls


60 150 N/A <1.0 N/A N/A Signif-icant

N/A N/A

NAS04944

Armstrong

1978

fresh prawn in 3 main daily meals combined, among cases / controls


60 150 N/A 0.7 N/A N/A <0.05 N/A Age, sex, SES, ethnicity/ race, area of residence, lifestyle factors

1 June, 2006


97

Preserved seafood: Adulthood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Salted seafood pastes

Yes vs. no FFQ - Study-specific


935 1032 2 1.44 No 0.97-2.15

0.07 N/A Age, sex, occupational exposure to fumes, education, smoking, environmental factors, other diseases

NAS01056

Lee

1994

dried oyster, during adulthood

Never to more than 3 times per month


Singa-pore


200 405 4 2.2 Never 0.6-7.3


NAS01056

Lee

1994

dried prawn, consumption during adulthood

Never to 3+ times per week


Singa-pore


199 406 5 1.5 Never 0.5-3.6


NAS01459

Yu

1989

salted shrimp paste, 3 years prior to diagnosis




N/A N/A

NAS01459

Yu

1989

salted shrimp paste, unsure time of consumption




N/A Area of residence, age, sex, salted fish, fermented fish sauce, moldy bean curd, chan pai mui, gar ink gee, tomatoes

NAS01608

Yu

1986

dried shrimp, subject's at 10 years of age or 3 years prior to diagnosis


China, Hong Kong




NAS01922

Ning

1990


Never to Weekly



100 300 3 1.8 Never 0.9-3.8


1 June, 2006


98

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

dried shrimp, 3 years prior to diagnosis




N/A N/A

Preserved seafood: Childhood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

prawn, dried, at age 10

Never to 1-3 times per week


Singa-pore


150 340 4 0.7 Never 0.3-1.4


NAS01056

Lee

1994

oyster, dried, at age 10



Singa-pore


151 342 4 1.1 Never 0.3-3.4


NAS01459

Yu

1989

salted shrimp paste, during ages 1-2

Rarely to weekly



110 138 3 N/A Rarely N/A N/A 0.07 Area of residence, age, sex, salted fish consumption during weaning

NAS01459

Yu

1989

salted shrimp paste, at age 10

Rarely to daily




NAS01520

Yu

1988

fermented crab paste, at age 10




N/A Age, sex

1 June, 2006


99

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01520

Yu

1988

fermented shrimp paste, at age 10




N/A Age, sex

NAS01520

Yu

1988

dried shrimp, at age 10




N/A Age, sex

NAS01608

Yu

1986



China, Hong Kong




NAS01922

Ning

1990





N/A N/A

NAS01922

Ning

1990





N/A N/A

NAS01922

Ning

1990

salted shrimp paste, at 10 years

None to weekly/ daily



100 300 4 3.2 None N/A 0.007 N/A Age, Sex, Area of residence, salted fish and carrot consumption at 10 years

2.5.4 Eggs Non-preserved eggs Case-control (4)

1 June, 2006


100

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00577

Yuan

2000

Eggs, fresh N/A FFQ - Study-specific



N/A N/A

NAS01459

Yu

1989

Eggs, at age 1-2 N/A FFQ - Study-specific




NAS01459

Yu

1989

Eggs, at age 10 N/A FFQ - Study-specific




NAS01459

Yu

1989

Eggs, 3 years prior to diagnosis





NAS01520

Yu

1988

fresh eggs during weaning




NAS01520

Yu

1988

fresh eggs, ages 1 to 2 years




NAS01520

Yu

1988

fresh eggs, at age 10




N/A Age, sex

NAS04944

Armstrong

1978

fresh eggs, at evening meal among families of cases and controls



N/A N/A

1 June, 2006


101

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS04944

Armstrong

1978

fresh egg in three main daily meals, among cases/ controls



N/A Age, sex, SES, ethnicity/ race, area of residence, lifestyle factors

NAS04944

Armstrong

1978

Fresh egg, for breakfast among families of partici-pants



N/A N/A


Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

r2 Ref group

CI P value

p value for trend

Adjusted for

NAS00817

Koo

1997

Eggs N/A Per capita consumption

China, Hong Kong


r2 = -.42


NAS00817

Koo

1997

Eggs N/A Per capita consumption

China, Hong Kong



r2 = -.14


Salted eggs: Adulthood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: salted eggs

Lowest to highest



89 113 2 2.0 N/A 1.2-3.2

N/A N/A Age, Sex, Ethnicity/ Race, Total calories, Subjects w/ mothers questionnaire

1 June, 2006


102

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Salted eggs, 5 years pre-diagnosis




282 282 3 2.55 Monthly 1.44-4.53


NAS00749

Armstrong

1998

Salted eggs, lifetime consumption, includes dietary information at age 10 and age 5 years prior to diagnosis





N/A 0.039 N/A SES, salted fish/ pork/ beef liver, recent consumption, shrimp/ chinese flowering cabbage/ oranges/ tangerines, lifetime consumption, beer

NAS01056

Lee

1994

Salted egg, during adulthood




200 406 4 1.4 Never 0.6-3.2


NAS01922

Ning

1990

salted chicken or duck egg, 3 years prior to diagnosis




N/A N/A

NAS04944

Armstrong

1978

salted egg in three main daily meals combined, among cases and controls




Salted eggs: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


103

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Salted eggs, consumption at age 10




282 282 3 2.4 Monthly 1.4-4.11

N/A N/A Unadjusted

NAS00749

Armstrong

1998







NAS01056

Lee

1994

salted egg, at age 10

Never to 3+ times per month



149 344 4 0.5 Never 0.2-1.5


NAS01520

Yu

1988

salted duck eggs, during weaning



128 174 2 5.0 No 1.2-21

0.06 N/A Age, sex

NAS01922

Ning

1990

salted chicken or duck egg, at age 10




N/A N/A

Preserved eggs Case-control (5) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


104

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Preserved eggs- not specified, but measured salted egg, fermented black egg





0.88-1.55

N/A 0.11 Age, sex, occupational exposure to fumes, education, smoking, environmental factors, other diseases

NAS01056

Lee

1994

Century egg, an unsalted preserved egg, at age 10

Never to 1-3 times per month



151 341 3 0.8 Never 0.4-1.6


NAS01056

Lee

1994

Century egg, an unsalted preserved egg, at adulthood




200 406 4 1.0 Never 0.3-3.8


NAS01113

Zheng

1994

Salted, dried and tinned eggs




N/A N/A

NAS01520

Yu

1988

pay dann - a kind of fermented duck egg, at age 10

Rarely to weekly




N/A Age, sex

NAS01922

Ning

1990

fermented duck egg, at 10 years of age




N/A N/A

NAS01922

Ning

1990

fermented duck egg, 3 years prior to diagnosis




N/A N/A

2.6 Fats, oils and sugars as foods

1 June, 2006


105


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Unspecified fat

Currently to 20 years ago



53 currently, 63 20 years ago


2 2.4 Not clear

0.87-6.56

Not signif-icant


NAS00424

Laouamri

2001

Dried, salted fat






2 9.25 Not clear

3.9-21.5

.001 N/A Age, sex, area of residence

NAS01056

Lee

1994

Cod-liver oil, during infancy




62 97 4 0.5 Never 0.1-2.0

Not signif-icant


NAS01056

Lee

1994

Cod-liver oil, at age 10




150 341 5 1.0 Never 0.5-1.9

Not signif-icant


NAS04944

Armstrong

1978

Use of cooking oils and fats



N/A Unadjusted

2.6.1 Animal fats (as foods) Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

1 June, 2006


106

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00424

Laouamri

2001

Butter used as a cooking medium

Currently and 20 years ago



current: 37

20 years ago: 56

current: 34

20 years ago: 64

2 Current: OR = 1.16;

20 years ago: OR = 0.42

N/A Current: 0.63-2.12;

20 years ago: 0.16-1.09

Not signif-icant


NAS00424

Laouamri

2001

Rancid butter used as a cooking medium

Currently and 20 years ago



current: 44

20 years ago: 59

current: 11

20 years ago: 44

2 Current: OR = 7.6;

20 years ago: OR = 4.0

N/A Current: 3.51-16.4;

20 years ago: 1.62-9.84

Current: 0.001;

20 years ago: 0.01


NAS01381

Jeannel

1990

Sheep’s tail fat, childhood




NAS06022

Wang

1993

Pork fat Frequent of less frequent

Question-naire


122 122 2 0.256 Less frequent

N/A .0253 N/A Age, sex, salted fish, plant oil, less whole-grain consumption, vegetable intake, coloured vegetables non-nutrient chemicals, environmental factors, high income

2.6.2 Plant oils (as foods) Case-control (4)

1 June, 2006


107

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Oils and fats used as a cooking medium: Sunflower oil




135 138 2 0.5 N/A 0.15-1.62


NAS00424

Laouamri

2001

Oils and fats used as a cooking medium: Olive oil




54 57 2 0.66 N/A 0.31-1.38


NAS00424

Laouamri

2001

Oils and fats used as a cooking medium: Vegetable fats




25 31 2 3.0 N/A 0.04-223


NAS00424

Laouamri

2001

Seasonings: vegetable fats




27 46 2 1.0 N/A Not signif-icant


NAS00424

Laouamri

2001

Seasonings: Olive oil




93 119 2 0.35 N/A 0.15-0.79


NAS01056

Lee

1994

margarine, at age 10

Never to >3 times a week



113 340 5 0.6 Never 0.3-1.1

N/A 0.03 Age, sex, education, ethnicity/ race

NAS01520

Yu

1988

fennel oil, at age 10




N/A N/A

1 June, 2006


108

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06022

Wang

1993

Plant oils Less frequently to frequently consumed

Question-naire


122 122 2 4.29 Less frequent

N/A 0.0019 N/A Sex, age, env factors, wholegrains, pork fat, salted fish, non-nutrient chemicals, high-income, vegetable intake, coloured vegetables

2.6.4 Sugars Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Piece of sugar, teething

Ever or never



36 24 2 2.2 Never 1.1-4.5


2.7 Milk and dairy products Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Powdered milk, duration of nursing

Never to 18 months



18 14 4 1.4 Never 0.44-4.43

Not signif-icant

Not signif-icant


1 June, 2006


109

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Animal milk, duration of nursing

Never to 12 months



18 10 3 2.33 Never 0.62-8.64

Not signif-icant

Not signif-icant


NAS00577

Yuan

2000

Fresh milk N/A FFQ - Study-specific



N/A Unadjusted

NAS01459

Yu

1989

Cow’s milk, age 10 or adult





NAS04944

Armstrong

1978

Milk With daily meals: yes or no


60 150 2 0.6 N/A N/A <0.01 N/A Age, sex, SES, ethnicity/ race, area of residence, lifestyle factors

NAS04944

Armstrong

1978

Milo, fortified and flavoured powdered milk drink

With daily meals: yes or no


60 150 2 1.0 N/A N/A Not signif-icant


NAS04944

Armstrong

1978

Horlicks, fortified and flavoured powdered milk drink





2.8 Herbs, spices, condiments Herbal, spices, and condiments: Childhood consumption Case-control (3)

1 June, 2006


110

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Herbs, spices, condiments, Dietary intake during childhood (at age 10) reported by subjects

Lowest to Highest



375 327 3 2.3 Lowest 1.1-4.7

N/A N/A Age, Sex, Ethnicity/ Race, Subjects w/ mothers questionnaire, Total calories

NAS01113

Zheng

1994

Herbal mixtures, weaning / childhood



88 176 N/A 1.8 N/A N/A 0.07 N/A N/A

NAS01520

Yu

1988

hot pepper paste, at age 10




N/A N/A

NAS01520

Yu

1988

soy sauce, at age 10




N/A N/A

NAS01520

Yu

1988

fish sauce, at age 10




N/A N/A

NAS01520

Yu

1988

oyster sauce, at age 10




N/A N/A

Herbal intake Case-control (6) Meta-analysis Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


111

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00544

Chelleng

2000

Herbal nasal drops

Yes vs. No

Unknown India Indian 141 Mean 44/ Mixed

47 94 2 58.4 No 7.9-430

0.0001 N/A Age, sex, ethnicity/ race, Area of residence, Alcohol habits, Smoking habits, type of house, number of windows, kitchen inside/outside, soot in living room, type of cooking fuel used, habit of chewing betel nut, smokeless tobacco use

NAS01153

West

1993

Herbal medicines consumption

Never vs. ever


104 205 2 2.5 Never 1.1-5.3

N/A N/A Sex, Age Processed meats, Fresh fish, Smoking Habits, Educational Level, Formaldehyde, Public vs. private hospital ward, Dust/exhaust, Burning anti-mosquito coils

NAS01251

Hildesheim

1992

herbal medicines

Never vs. ever


Philippines Filipino 309 N/A/ Mixed

104 205 2 2.6 Never 1.4-4.6

N/A N/A Age, Sex, Area of residence, Smoking, Educational Level, Chinese ancestry, Salted Fish

NAS01593

Lin

1986

Use of herb drug

Never to usual

Unknown China Chinese 1360 N/A/ Mixed

343 1017 3 11.7 N/A N/A N/A N/A Smoking Habits, Titer of antibodies to EB virus capsid antigen, Use of nasal baim or oil, Poor ventilation, Place of birth Mainland China or Taiwan

NAS04917

Lin

1973

Herb drugs Reference to frequently

Interview China, Taiwan


343 1017 3 3.51 N/A N/A N/A N/A Age, Sex, Nativity

1 June, 2006


112

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04928

Henderson

1976

Use of medicinal soups (herbs concocted in teas or soups used in traditional Chinese medicine for curative purposes)

Yes vs no Interview United States

Various 423 Mean 52/ Mixed

156 267 2 0.5 No N/A 0.04 N/A Age, race, area of residence, ethnicity/ race, SES

Non-preserved spice intake Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00424

Laouamri

2001

Black pimento, used at least once a week

>1 time a week: yes or no




NAS00424

Laouamri

2001

Mint, at least once per week





NAS01812

Geser

1978

vinegar N/A FFQ - Study-specific

China, Hong Kong



N/A Age, sex, Use of ancestral alters and Buddhist alters, Oyster soy, Xanthozylon Seeds, Flavor Essence, Mustard Paste, Chinese Wine, Bread

1 June, 2006


113

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS04944

Armstrong

1978

sauces, for dinner among families of participants



N/A N/A

Preserved spice intake Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Harissa (chili peppers, dried then pickled and preserved in olive oil with garlic), at least once per week




72 72 2 5.0 No N/A <.001 N/A Age, sex, area of residence

NAS00424

Laouamri

2001

Seasonings: Dried Peppers




72 72 2 5.5 N/A 2.55-11.8


NAS00424

Laouamri

2001

Seasonings: Pickled Peppers




72 72 2 2.85 N/A 1.25-6.45


NAS00531

Ward

2000

Adult Dietary Intake: hot chili sauce

Lowest to Highest



375 327 2 1.4 Lowest 0.9-2.1

N/A N/A Age, Sex, Ethnicity/ Race, Subjects w/ mothers question-naire, Total calories

NAS01812

Geser

1978

Households w/ NPC patients and of controls: mustard paste


China, Hong Kong


144 143 2 0.44 No 0.26-0.74

N/A N/A Age, sex

1 June, 2006


114

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01812

Geser

1978

Households w/ NPC patients and of controls: chilli sauce


China, Hong Kong


144 144 2 0.41 No 0.24-0.69

N/A N/A Age, sex

NAS01812

Geser

1978

Mustard paste N/A FFQ - Study-specific

China, Hong Kong



N/A Age, sex, Use of ancestral alters and Buddhist alters, Vinegar, Xanthozylon Seeds, Flavor Essence, Oyster Soy, Chinese Wine, Bread

NAS04944

Armstrong

1978

pickled chili, in three main daily meals combined, among cases and controls

Yes or no Recall Malaysia Chinese 210 25-81/ Mixed

60 150 2 0.3 N/A N/A <.01 N/A Age, sex, ethnicity/ race,SES, household type, area of residence

Soy sauce Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Soy sauce (see yao)




N/A N/A

NAS01813

Shanmugaratnam

1978

Soya Sauce (Ear, Nose, and Throat Department controls)

Less than once daily to more than twice daily


Singapore Chinese 2018 N/A/ Mixed


N/A Age, Sex, interviewer

1 June, 2006


115

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01813

Shanmugaratnam

1978

Soya Sauce (Non-ENT hospital controls)






NAS04944

Armstrong

1978

thin soya sauce, in three main daily meals combined, among cases and controls



N/A Age, sex, ethnicity/ race,SES, household type, area of residence

NAS04944

Armstrong

1978

thin soya sauce, for breakfast among families of participants



N/A N/A

Other fermented condiment intake Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Fish sauce (yu lo)




N/A N/A

NAS00577

Yuan

2000

Oyster sauce (ho yao)




N/A N/A

NAS01812

Geser

1978

Oyster Soy


China, Hong Kong



N/A Age, sex, Use of ancestral alters and Buddhist alters, Vinegar, Xanthozylon Seeds, Flavor Essence, Mustard Paste, Chinese Wine, Bread

1 June, 2006


116

2.9 Composite foods Mixed vegetables Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Fresh green beans and peas





0.62-0.99


NAS00700

Farrow

1998

labeled yellow vegetables and includes winter squash, carrots, yams

Lowest to highest

FFQ - Block

United States

American 345 18-74/ Mixed

140 208 4 0.59 lowest 0.29-1.22

N/A 0.21 Age, Sex, Alcohol consumption, Smoking Habits, Energy Intake

NAS00749

Armstrong

1998

carrots/ sweet potatoes; 5 years pre-diagnosis




282 282 3 0.48 Monthly 0.28-0.83

N/A 0.02 Unadjusted

NAS00749

Armstrong

1998

carrots, sweet potatoes, at age 10




282 282 3 0.67 Monthly 0.33-1.27

N/A N/A Unadjusted

NAS00749

Armstrong

1998

green beans/ peas, 5-years pre-diagnosis




282 282 3 0.60 Monthly 0.37-0.98


NAS00749

Armstrong

1998

green beans/ peas, consumption at age 10




282 282 3 0.88 Monthly 0.47-1.62

N/A N/A Unadjusted

Foods with sauces or pastes

1 June, 2006


117


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Hot sauce 3-4 times a week with stews

3-4 times a week: yes or no



72 72 2 11.3 No 4.2-28.5

Signif-icant


NAS00424

Laouamri

2001

Hot sauce 3-4 times a week with fried foods




72 72 2 5.5 No 2.2-14.0

Signif-icant


NAS00424

Laouamri

2001

Hot sauce 3-4 times a week with pulses




72 72 2 4.5 No 2.0-9.9

Signif-icant


NAS00424

Laouamri

2001

Hot sauce 3-4 times a week with couscous




72 72 2 12.5 No 4.1-37.9

Signif-icant


NAS00424

Laouamri

2001

Hot sauce 3-4 times a week with pasta




72 72 2 8.0 No 1.4-45.8

Signif-icant


NAS00424

Laouamri

2001

Hot sauce 3-4 times a week with bread and butter




72 72 2 6.0 No 0.6-60.5

Not signif-icant


NAS00424

Laouamri

2001

Hot sauce 3-4 times a week with salad




72 72 2 7.0 No 0.8-60.6

Not signif-icant


NAS01056

Lee

1994

chinese rojak, salad containing prawn paste, at age 10




64 102 4 0.9 Never 0.3-2.2


1 June, 2006


118

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

chinese rojak, a salad containing prawn paste, during adulthood

Never to > 3 times per month



64 102 4 1.6 Never 0.4-5.9

N/A N/A Age, sex, education, ethnicity/ race

NAS01056

Lee

1994

belachan, prawn and chilli paste, at age 10

Never to > 3 times per week



64 102 5 1.8 Never 0.6-5.3

N/A N/A Age, sex, education, ethnicity/ race

NAS01056

Lee

1994

belachan, prawn and chilli paste, during adulthood




N/A N/A

NAS01381

Jeannel

1990

Dietary Intake During Weaning: Harissa, olive oil and bread

Less than once a month to more than twice a week



80 160 4 6.5 Less than once a a month

N/A N/A N/A Sex, age, lifestyle factors, area of residence

Foods with rice or noodles Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01113

Zheng

1994

Salted fish in rice porridge, before the age of 2

Rarely to monthly and weekly



88 176 3 3.8 Rarely 1.5-9.8

.005 N/A Age, Sex, Area of residence, Socio-demographic score made up of housing in childhood and the presence of windows and monthly income the year before diagnosis, Use of wood fuel in the year before diagnosis, consumption of herbal tea in the year before diagnosis

1 June, 2006


119

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01113

Zheng

1994

Salted fish in rice porridge, between the ages of 2 and 10

Rarely to monthly and weekly



88 176 3 3.2 Rarely N/A 0.003 N/A Age, Sex, Area of residence, Socio-demographic score made up of housing in childhood and the presence of windows and monthly income the year before diagnosis

NAS04944

Armstrong

1978

a dish of rice or noodles either with fish, prawns, pork, chicken or egg, with vegetables and sauces, sometimes in a soup, for lunch among families of participants


60 150 2 N/A N/A N/A Not significant

N/A Unadjusted

NAS04944

Armstrong

1978

rice with fish, pork, chicken or egg, for evening meal among families of participants



N/A Unadjusted

‘Cooling drink’ Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

Cooling soup, a popular medicinal drink, at age 10





1 June, 2006


120

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

Cooling soup, a popular medicinal drink, at 3 years prior to diagnosis





NAS01520

Yu

1988

cooling soup, at age 10




N/A Age, sex

NAS01608

Yu

1986

cooling soup, at 10 years of age or 3 years prior to diagnosis





NAS01813

Shanmugaratnam

1978

'Cooling' drink (ENT Hospital controls)

Never or unknown to weekly or more



379 1639 3 1.282 Never or known



NAS01813

Shanmugaratnam

1978

‘Cooling' drink (non-ENT hospital controls)

Never or unknown to weekly or more



379 1639 3 1.087 Never or known



Preserved composite foods Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS00577

Yuan

2000

All preserved food and fresh oranges/ tangerines

High to low preserved by high to low citrus



935 1032 9 3.19 Low preserved, high citrus

2.08-4.91

Signif-icant

N/A Age, sex, occupational exposure to fumes, education, smoking, environmental factors, other diseases

1 June, 2006


121

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01056

Lee

1994

salted beef or malt extract, during infancy

Never to > 3 times per week



62 95 4 0.3 Never 0.05-1.6


NAS01812

Geser

1978

Households of NPC patients / controls: Tinned food w/ fish


China, Hong Kong


150 150 2 0.46 No 0.23-0.94

N/A N/A Age, sex

NAS04928

Henderson

1976

Salted snacks Yes vs. no Interview United States


156 267 2 0.4 No N/A 0.03 N/A Age, race, area of residence, ethnicity/ race

Other composite foods Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01381

Jeannel

1990

Dietary Intake During Weaning: Stewing mixture (red pepper, black pepper, caraway, coriander, oil, salt and garlic)



80 160 2 8.4 No N/A <0.005 N/A Sex, age, lifestyle factors, area of residence

NAS01381

Jeannel

1990

Dietary Intake During Preceding Year to Diagnosis: Stewing mixture (red pepper, black pepper, caraway, coriander, oil, salt and garlic)



80 160 2 4.4 No N/A 0.04 N/A Sex, age, lifestyle factors, area of residence

1 June, 2006


122

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS04944

Armstrong

1978

dumpling, for breakfast among families of participants


60 150 N/A N/A N/A N/A Case families had dumplings significantly more often at breakfast

N/A Unadjusted

NAS04944

Armstrong

1978

soup, at evening meal among families of participants


60 150 2 N/A N/A N/A Case families ate soup significantly less often at evening meal

N/A Unadjusted

NAS04944

Armstrong

1978

Dumplings in three main daily meals combined, among families of participants


60 150 2 1.1 No N/A Not significant N/A Sex, Age, race, Household type, census district, Socio-economic status

3.1 Total fluid intake Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS04944

Armstrong

1978

Drinks for breakfast


60 150 2 N/A N/A N/A Case families had drinks significantly less often at breakfast

N/A Unadjusted

3.2 Water Case-control (2)

1 June, 2006


123

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Type of drinking: water supply

Spring, individual well, collective well, piped



72 85 4 Well: OR = 7.0

Piped: OR = 0.2

Spring Well: 0.8-60.7

Piped: 0.05-0.78

Not signif-icant

0.05


NAS04944

Armstrong

1978

Water with 3 daily meals combined


60 150 2 OR = 1.4

N/A N/A <.01 N/A Age, sex, ethnicity/ race,SES, household type, area of residence

3.3 Milk as beverage Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Powdered milk, duration of nursing

Never to 18 months



18 14 4 1.4 Never 0.44-4.43

Not signif-icant

Not signif-icant


NAS00424

Laouamri

2001

Animal milk, duration of nursing

Never to 12 months



18 10 3 2.33 Never 0.62-8.64

Not signif-icant

Not signif-icant


NAS00577

Yuan

2000

Fresh milk N/A FFQ - Study-specific



N/A Unadjusted

1 June, 2006


124

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

Cow’s milk, age 10 or adult





NAS04944

Armstrong

1978

Milk With daily meals: yes or no


60 150 2 0.6 N/A N/A <0.01 N/A Age, sex, SES, ethnicity/ race, area of residence, lifestyle factors

NAS04944

Armstrong

1978

Milo, fortified and flavoured powdered milk drink





NAS04944

Armstrong

1978

Horlicks, fortified and flavoured powdered milk drink





3.5 Fruit juices Case-control (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

Orange juice, at age 10




282 282 3 0.60 Monthly 0.17-2.15

Not significant


NAS00749

Armstrong

1998

Orange juice, 5 prior to diagnosis




282 282 3 0.85 Monthly 0.51-1.42

N/A .047 Age, sex, area of residence

1 June, 2006


125

3.6 Hot drinks Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS04944

Armstrong

1978

Coffee or tea for breakfast


60 150 2 N/A N/A N/A Not different between case families and controls

N/A Unadjusted

3.6.1 Coffee Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01639

Mabuchi

1985

Coffee At least 1 cup a day

Unknown United States

Various 78 16-79/ Mixed

29 32 2 N/A <1 cup a day


N/A Age, sex, ethnicity/ race, marital status

NAS01639

Mabuchi

1985

Caffeine-free coffee

At least 1 cup a day



4 8 2 N/A <1 cup a day



NAS04928

Henderson

1976

Any use of coffee

No use or any use

Interview United States


156 267 2 1.1 No use

N/A 0.49 N/A Age, race, area of residence, ethnicity/ race, SES

NAS04944

Armstrong

1978

Coffee with 3 main daily meals


60 150 2 0.8 N/A N/A 0.05 N/A Age, sex, area of residence, household type, SES , ethnicity/ race

1 June, 2006


126

3.6.2 Tea Tea: Adulthood consumption Case-control (7) Meta-analysis Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01113

Zheng

1994

Herbal tea, in the year before diagnosis

Yes vs. no



88 176 2 4.2 No 1.3-13

0.02 N/A Age, Sex, Area of residence, Socio-demographic (housing in childhood/ windows, monthly income the year before diagnosis) Use wood fuel in the year before diaganosis, Salted fish in rice porridge before the age of 2

NAS01639

Mabuchi

1985

Tea, at least one cup per day

< 1 cup per day to ≥ 1 cup per day



39 39 2 N/A No N/A Not significant


NAS01813

Shanmugaratnam

1978

Chinese Tea (ENT hospital controls)

Less than once monthly to daily





NAS01813

Shanmugaratnam

1978

Chinese Tea (Non-ENT hospital controls)

Less than once monthly to daily





NAS04917

Lin

1973

Drinking of tea

N/A Interview China, Taiwan



N/A N/A

1 June, 2006


127

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS04928

Henderson

1976

Any use of tea

Any use vs no use



156 267 2 0.5 No use

0.3-1.0

0.02 N/A Age, sex, area of residence, ethnicity/ race, SES

NAS04944

Armstrong

1978

tea, with three main daily meals, among cases / controls

N/A Recall: interview


N/A N/A N/A 0.5 N/A N/A < .01 N/A Sex, Age, Household type, SES, Census district, Ethnicity/ Race

NAS06023

Zou

1999

Tea < 1 cup per day to ≥ 1 cup per day



96 192 2 1.1 < 1 cup per day

0.6-2.2


Tea: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Cumin, (at least 3 times a week for at least 1 month) to newborn, in terms of infusions or herb teas


Algeria Unknown 144 9-70/ Mixed

72 72 2 1.35 No 0.71-2.63


NAS00424

Laouamri

2001

Olive oil, (at least 3 times a week for at least 1 month) to newborn, in terms of infusions or herb teas



72 72 2 0.84 No 0.34-1.97


1 June, 2006


128

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Bay leaf, (at least 3 times a week for at least 1 month) to newborn: in text notes that this is bay leaf tea



72 72 2 3.0 No 2.93-5.23


NAS00424

Laouamri

2001

Fenu-greek, (at least 3 times a week for at least 1 month) to newborn, in terms of infusions or herb teas



72 72 2 2.0 No 0.51-7.78


NAS00424

Laouamri

2001

Aniseed, (at least 3 times a week for at least 1 month) to newborn, in terms of infusions or herb teas



72 72 2 1.66 No 0.09-28.3


3.6.2.2 Green tea Case-control (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01812

Geser

1978

Green tea


China, Hong Kong


150 150 2 0.57 No N/A 0.05 N/A Age, sex

3.7 Alcoholic drinks Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


129

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00898

Vaughan

1996

Comparison of wine and liquor consumption with beer consumption among ever drinkers

Beer, wine, or liquor


United States


66 166 3 Wine: OR = 1.6

Liquor: OR = 0.9

Beer Wine: 0.4-6.4

Liquor: 0.4-2.1

Not signif-icant

Not signif-icant

N/A Age, sex, clinic site, education, smoking, alcohol consumption

3.7.1 Total alcoholic drinks Cohort (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

SIR Ref group CI P value p value for trend

Adjusted for

NAS00381

Boffetta

2001

Alcoholic Alcoholics v. non-alcoholics

Unknown Sweden Swedish 173665 N/A/ Mixed

21 N/A 2 1.56 Non-alcoholics

0.97-2.39

Not signif-icant

N/A Age, sex, calendar year


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


130

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00576

Yuan

2000

Weekly alcohol drinking



935 1032 2 0.8 No O,64-1.01

N/A N/A Sex, Age, Exposure to smoke from heated rapeseed oil/ burning coal while cooking, Preserved foods and oranges/ tangerines, Family history of Cancer, Occupational exposure to chemical fumes, Smoking, Edu Level, History of chronic ear/ nose condition

NAS00576

Yuan

2000

Total Alcoholic Drinks

None to ≥ 29 drinks per week



935 1032 4 1.04 None 0.73-1.46

N/A N/A Sex, Age, Exposure to smoke from heated rapeseed oil and burning coal while cooking, Preserved foods and oranges/ tangerines, Family history of Specific Cancer, Occupational exposure to chemical fumes, Smoking Habits, Educational Level, History of chronic ear and nose condition

NAS00612

Cheng

1999

Alcohol consumption; Drinking habit

Ever vs, Never

Unknown China Chinese 702 15-74/

Mixed 375 327 2 0.9 Never 0.6-

1.3 N/A N/A Age, Sex,

Ethnicity/ Race, Smoking Habits, family history of NPC, Educational Level

1 June, 2006


131

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00612

Cheng

1999

Drinking status

Never to current


Mixed 375 327 3 0.8 Never 0.6-

1.2 N/A 0.3 Age, Sex,


NAS00612

Cheng

1999

Alcohol consumption: Age starting alcohol drinking

Never to ≥ 25 Unknown


375 327 3 0.8 Never 0.5-1.3

N/A 0.4 Age, Sex, Ethnicity/Race, Smoking Habits, family history of NPC, Educational Level

NAS00612

Cheng

1999

Alcohol consumption: duration of alcohol drinking

None to ≥ 15 gram*years


Mixed 373 323 3 1.1 None 0.7-

1.6 N/A 0.9 Age, Sex,


NAS00612

Cheng

1999

Alcohol consumption: cumulative alcohol consumption (gram-year)

None to ≥ 2000 grams per month


Mixed 373 322 4 1.2 None 0.7-

2.2 N/A 1.0 Age, Sex,


NAS00612

Cheng

1999

Alcohol consumption quantity

None to 60 grams per month


Mixed 374 324 3 1.1 None 0.7-

1.7 N/A 0.9 Age, Sex,


NAS00640

Nazar-Stewart

1999

Alcohol use < 2 drinks per day to ≥ 2 drinks per day


Multi-ethnic

225 18-74/ Mixed

80 139 2 1.6 < 2 drinks per day

0.82-3.12

N/A N/A Unadjusted

1 June, 2006


132

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00821

Hildesheim

1997

Consumption of alcohol

None to > 2 drinks per week

Unknown China, Taiwan


364 318 3 0.92 None 0.58-1.4

N/A N/A Age, sex

NAS00898

Vaughan

1996

Alcohol Use ≤ 6 drinks per

week to ≥ 21 drinks per week


United States


175 237 4 2.0 ≤ 6 drinks per week

1.0-4.0

N/A 0.15 Age, sex, clinic site, education, smoking

NAS01113

Zheng

1994

Alcoholic drinks




N/A N/A

NAS01141

Zheng

1994

Alcohol habits N/A FFQ - Study-specific



N/A N/A

NAS01248

Sriamporn

1992

Alcohol Intake Yes vs. no FFQ - Study-specific


120 120 2 1.5 No 0.7-3.4

N/A N/A Age, sex, area of residence, smoking, alcohol, occupation, Educational Level

NAS01254

Nam

1992

Alcohol consumption

≤3 drinks per

week to ≥24 drinks per week

Question-naire

United States

White 612 Mean 54/ Mixed

204 408 3 1.8 ≤3 drinks per week

1.1-3.1

N/A N/A Sex, Smoking habits

1 June, 2006


133

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01254

Nam

1992

Alcohol and cigarette consumption

≤ 3 drinks/

week and ≤ 30 pack-years of smoking to ≥ 24+ drinks/ week and ≥ 60 pack-years of smoking

Question-naire

United States

White 612 Mean 54/ Mixed

204 408 9 5.2 ≤ 3 drinks per week and ≤ 30 pack-years of smoking

N/A < 0.01

N/A Sex

NAS01410

Chen

1990

Years of Alcohol Consumption, among men

None to > 30 years

Question-naire


238 238 4 1.84 None 0.97-3.47

N/A N/A Age, Sex

NAS01495

Vaughan

1989

Alcohol Use ≤ 6 drinks/

week to ≥ 21 drinks/ week


N/A 573 20-74/ Mixed

21 552 3 2.43 ≤ 6 drinks per week

0.43-9.32

0.17 N/A Age, Sex

NAS01630

Yu

1985

Alcohol consumption

Rarely to Daily


100 100 4 2.8 Rarely N/A N/A N/A Age, Sex, Race and ethnicity, Area of residence

NAS01639

Mabuchi

1985

Alcohol consumption

≥ 1 drink/ day to < 1 drink/ day



25 26 2 N/A < 1 drink per day



NAS01712

Armstrong

1983

Alcohol N/A Unknown Malaysia Chinese 200 Mean 43/ Mixed


N/A N/A

1 June, 2006


134

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01813

Shanmugar-atnam

1978

Alcohol (v. ENT hospital controls)

Never to daily FFQ - Study-specific




NAS01813

Shanmugar-atnam

1978

Alcohol (v. non-ENT hospital controls)

Never to daily FFQ - Study-specific




NAS01922

Ning

1990

Use of alcohol N/A FFQ - Study-specific


100 300 N/A N/A N/A N/A 0.97 N/A Age, Sex, Area of Residence

NAS05679

Yang

2005

Alcohol Years of consumption prior to diagnosis





NAS06023

Zou

1999

Total Alcoholic Drinks

Yes vs. No Dietary History question-naire


70 160 2 0.9 No 0.5-1.9


3.7.1.1 Beers Case-control (3) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Beers Less than monthly to more than weekly




N/A 0.023 N/A SES, salted fish consumption

1 June, 2006


135

NAS01639

Mabuchi

1985

Ale-beer At least one per day





NAS04928

Henderson

1976

Beer Any use Interview United States


156 267 2 1.0 No use N/A 0.48 N/A Age, sex, area of residence, ethnicity/ race, SES

3.7.1.2 Wines Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS01639

Mabuchi

1985

Wine At least 1 glass a day



13 18 2 N/A No N/A Not significant


NAS01812

Geser

1978

Chinese wine


China, Hong Kong


150 150 2 N/A N/A N/A Stated in text as significant

N/A Age, sex, other foods, lifestyle factors

NAS04917

Lin

1973

Wine Drinking of wine

Interview China, Taiwan



N/A N/A

NAS04928

Henderson

1976

Wine Any use Interview United States


156 267 2 0.7 No use

0.4-1.1

0.05 N/A Age, sex, area of residence, ethnicity/ race, SES

3.7.1.3 Spirits Case-control (3)

1 June, 2006


136

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

Spirits Low, medium, high


Malaysia Chinese 564 Mean 45/ Mixes

282 282 3 Med: OR = 1.28

High: OR = 2.92

Low Med: 0.74-2.22

High: 1.05-8.14

Not signif-icant

Signif-icant

,008 Unadjusted

NAS01639

Mabuchi

1985

Whiskey At least 1 glass a day



7 15 2 N/A No N/A <0.05 N/A Age, sex, ethnicity/ race, marital status

NAS04928

Henderson

1976

Any liquor

Any use Interview United States


156 267 2 1.2 No use

N/A 0.31 N/A Age, sex, area of residence, ethnicity/ race, SES


Author, Yr


Asses-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Con-trols

No.

categories

r2 Ref group

CI P value

p value for trend

Adjusted for

NAS03683

Longnecker

1981

Spirits Per-capita Per-capita consumption

United States

Various N/A N/A/ Male N/A N/A N/A r2 = 0.21

N/A N/A <.001 N/A Age, ethnicity/ race

NAS03683

Longnecker

1981

Spirits Per-capita Per-capita consumption

United States

Various N/A N/A/ Female

N/A N/A N/A r2 = 0.01

N/A N/A >.05 N/A Age, ethnicity/ race

3.7.1.4 Other alcoholic drinks Case-control (1) Study Exposure Exposure Assessment Country Ethnicity No of

subjects Age/Sex No. No. No. OR Ref CI P value p value

for Adjusted for

1 June, 2006


137

identifier

Author, Yr

range Tool of subjects

analysed of subjects cases controls categories group trend

NAS01639

Mabuchi

1985

Mixed drinks

At least 1 drink per day



18 16 2 N/A None N/A Not signif-icant


4.1.2 Chemical contaminants Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Categories

OR Ref group


Adjusted for

NAS01141

Zheng

1994

Drinking of polluted water




N/A N/A

NAS01190

Zheng

1993

Drinking of polluted water


China Chinese 410 N/A/ Mixed 205 205 N/A N/A N/A N/A < 0.001 N/A N/A

4.1.2.7.1 Cadmium Case-control (2) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Mean/ Median

Ref group

CI P value

p value for trend

Adjusted for

NAS02012

Ling-Wei

1988

Cadmium Median exposure cases vs. controls

Unknown-NA

China Chinese 75 N/A/ N/A 45 30 Median exposure cases vs. controls

Median cases: 0.42

Median controls: 0.05

N/A 0.01 N/A Unadjusted

1 June, 2006


138

NAS06012

Deng

1995

measured in serum Cd concentration

Mean exposure cases vs. controls

Serum level, measured by colorimeter


44 42 Mean exposure cases vs. controls

Mean cases: 5.29

Mean controls: 3.57

Cases: 4.6-5.98

Controls: 2.31-4.83


NAS06012

Deng

1995

concentration in rice


N/A China Chinese 86 20-60/ Mixed


Mean cases: 34.46

Mean controls: 24.96

N/A <0.05 N/A Unadjusted

NAS06012

Deng

1995

Cd concentration in drinking water




Mean cases: 0.3

Mean controls: 0.25

N/A >0.05 N/A Unadjusted

4.1.2.7.2 Arsenic Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Means Ref group CI P value

p value for trend

Adjusted for

NAS02696

Man

1996

Arsenic detected in hair sample


Hair Sample

China Unknown 124 30-69/ N/A


Mean cases: 0.195 ppm

Mean controls: 0.133 ppm



Author, Yr


Assessment

Tool

Country Ethnicity

of subjects

No of popula-tions analysed

Age/Sex of subjects

No.

cases

No.

Con-trols

No.

Cate-gories

SMR Ref group

CI P value

p value for trend

Adjusted for

NAS00617

Tsai

1999

Arsenic in Artesian wells

N/A assessment of arsenic in artesian well water was done in previous studies

China, Taiwan

Chinese 4 N/A/ Male

60 N/A N/A 1.10 N/A 0.84-1.41

Not signif-icant

N/A Unadjusted

1 June, 2006


139

Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Con-trols

No.

Cate-gories

SMR Ref group

CI P value

p value for trend

Adjusted for

NAS00617

Tsai

1999

Arsenic in Artesian wells

N/A assessment of arsenic in artesian well water was done in previous studies

China, Taiwan

Chinese 4 N/A/ Female

29 N/A N/A 1.30 N/A 0.87-1.86

Not signif-icant

N/A Unadjusted

NAS01383

Chen

1990

Arsenic in drinking water

N/A arsenic level in waters of 83,656 wells was determined by a special survey team; standard mercuric bromide stain method

China, Taiwan


N/A N/A N/A N/A N/A N/A Not signif-icant

N/A Age

NAS01434

Wu

1989

Arsenic in well water

< 30 to 60+ mg/L?

arsenic concentration in drinking water

China, Taiwan

Chinese 3 N/A/ Male

11 N/A 3 Event rate = 8.58/ 100000/ year


N/A Age

NAS01434

Wu

1989

Arsenic in well water

< 30 to 60+ mg/L?

arsenic concentration in drinking water

China, Taiwan

Chinese 3 N/A/ Female

7 N/A 3 Event rate = 4.89/ 100000/ year


N/A Age

4.1.2.7.3 Other heavy metals Lead Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Controls

No.

Cate-gories

Means Ref group

CI P value

p value for trend

Adjusted for

NAS01865

Robinson

1968

Lead, in maize leaf


Unknown/NA Kenya Central Bantu and Nilo-Hamitic

100 N/A/ N/A 50 50 2 Mean cases: 2.08

Mean controls: 2.14


N/A Area of residence

1 June, 2006


140

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Controls

No.

Cate-gories

Means Ref group

CI P value

p value for trend

Adjusted for

NAS02012

Ling-Wei

1988

Lead, in drinking water

Median exposure cases vs. controls

Unknown/NA China Chinese 75 N/A/ N/A 45 30 2 Median cases: 6.4



NAS02696

Man

1996

lead, detected in hair sample


Hair Sample China Unknown 124 30-69/ N/A

29 95 2 Mean cases: 5.58 ppm



N/A Unadjusted

Mercury Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Controls

No.

Cate-gories

Means Ref group CI P value

p value for trend

Adjusted for

NAS02696

Man

1996

mercury, detected in hair sample


Hair Sample


29 95 2 Mean cases: 3.45 ppm

Mean controls: 2.75


N/A Unadjusted

Molybdenum Case-control (2) Study identifier

Author, Yr


Asses-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Controls

No.

Cate-gories

Means Ref group

CI P value

p value for trend

Adjusted for

NAS01865

Robinson

1968

Molybdenum, in maize leaf


Unknown Kenya Central Bantu and Nilo-Hamitic

100 N/A/ N/A 50 50 2 Mean cases: 1.91

Mean controls: 1.69



1 June, 2006


141

Study identifier

Author, Yr


Asses-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Controls

No.

Cate-gories

Means Ref group

CI P value

p value for trend

Adjusted for

NAS06012

Deng

1995

serum Molybdenum concentration




44 42 2 Mean cases: 18.39

Mean controls: 26.7

Cases: 16.4-22.2

Controls: 20.8-32.6


NAS06012

Deng

1995

Molybdenum concentration in rice



44 42 2 Mean cases: 136.07



NAS06012

Deng

1995

Molybdenum concentration in drinking water



44 42 2 Mean cases: 0.41

Mean controls: 0.71


Nickel Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects

No of sub-jects ana-lysed

Age/ Sex of sub-jects

No.

cases

No.

Controls

No.

Cate-gories

Means Ref group


Adjusted for

NAS01865

Robinson

1968

Nickel, in maize leaf


Unknown Kenya Central Bantu and Nilo-Hamitic

100 N/A/ N/A

50 50 2 Mean cases: 1.33

Mean controls: 1.29



NAS06012

Deng

1995

serum Nickel (Ni) concentration




44 42 2 Mean cases: 66.59


Cases: 55-78.2

Controls: 32.3-50.5


NAS06012

Deng

1995

Nickel (Ni) concentration in rice



44 42 2 Mean cases: 170.82



1 June, 2006


142

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects

No of sub-jects ana-lysed


No.

cases

No.

Controls

No.

Cate-gories

Means Ref group


Adjusted for

NAS06012

Deng

1995

Nickel (Ni) concentration in drinking water



44 42 2 Mean cases: 1.85

Mean controls: 1.14


4.1.2.9 Other contaminants Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Childhood Dietary Intake Age 3: Nitrosamines from soybean products, smoked

Lowest to highest



375 327 4 0.7 Lowest 0.3-1.8

N/A N/A Age, Sex, Ethnicity/ Race, Vegetable intake

NAS00531

Ward

2000

Dietary Intake During Weaning: Nitrosamines from soybean products, smoked

Lowest to highest



375 327 4 0.8 Lowest 0.4-1.8


NAS00531

Ward

2000

Childhood Dietary Intake Age 10: Nitrosamines from other foods, smoked

Lowest to highest



375 327 4 2.2 Lowest 0.8-5.6


NAS00531

Ward

2000

Childhood Dietary Intake Age 3: Nitrosamines from other foods, smoked

Lowest to highest



375 327 4 2.6 Lowest 1.0-7.0


1 June, 2006


143

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Childhood Dietary Intake During Weaning: Nitrosamines from other foods, smoked

Lowest to highest



375 327 4 3.9 Lowest 1.4-10.4


NAS00531

Ward

2000

Mother's intake of nitrosamines during breastfeeding: from soybean products, smoked

Lowest to highest



375 327 4 0.6 Lowest 0.2-1.4


NAS00531

Ward

2000

Mother's intake of nitrosamines during breastfeeding: from other products, smoked

Lowest to highest



375 327 4 1.4 Lowest 0.5-3.6



Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Con-trols

No.

Cate-gories

Regression Slope

Ref group

CI P value

p value for trend

Adjusted for

NAS00384

Takahashi

2001

Flouridation in drinking water

N/A water flouridation data were obtained from the Fluoridation Census 1985

United States

Various 9 N/A/ Male

Incidence rate = 1.51 over 15 years

N/A N/A 0.089 N/A N/A .049 N/A Age

NAS00384

Takahashi

2001

Flouridation in drinking water

N/A water flouridation data were obtained from the Fluoridation Census 1985

United States

Various 9 N/A/ Female

Incidence rate = 2.73 over 15 years

N/A N/A 0.217 N/A N/A .024 N/A Age

4.2 Preservation (preserved foods) Preserved animal foods

1 June, 2006


144

Preserved meat: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Dried, salted meat




72 72 2 4.75 N/A 1.8-12.5


NAS00577

Yuan

2000

Preserved Meats (not specified: ham, cured duck, salted pork)





1.12-2.79

N/A 0.56 Age, sex, area of residence, environ-mental factors, smoking, chemical fumes, history of ear/nose condition

NAS01056

Lee

1994

rou gan, dried sweetened meat, during adulthood




N/A Age, sex, ethnicity/ race, education, belachan, mei chye, canned, salted, & pickled vegetables, vitamin C, salted soy beans, sze chuan chye, kiam chye, vitamin E

NAS01113

Zheng

1994

Salted dried and tinned meat




N/A N/A

Preserved meat: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

rou gan, dried sweetened meat, usually pork, at 10 years old

Never to >1 times per week



149 342 3 0.8 Never 0.2-3.0


1 June, 2006


145

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01381

Jeannel

1990

Intake Before Weaning: Quaddid (spiced dried meat stored in oil)




NAS01381

Jeannel

1990

Intake During Weaning: Quaddid (spiced dried meat stored in oil)




80 160 3 2.8 <1 time a month


Preserved fish (excluding salted fish) Cohort (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

Chi-square

Ref group

CI P value

p value for trend

Adjusted for

NAS06011

Zou

1994






Not exposed


NAS06011

Zou

1994






Not exposed


NAS06011

Zou

1994






Not exposed



Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

1 June, 2006


146

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

Preserved cuttlefish, adult




198 305 4 1.3 Never 0.5-2.9

Not signif-icant


NAS01056

Lee

1994

Preserved cuttlefish, at age 10




146 341 4 0.6 Never 0.1-1.8

Not signif-icant


NAS01056

Lee

1994

Preserved fish tidbits, adult




198 406 4 2.6 Never 0.6-10.0

Not signif-icant


NAS01056

Lee

1994

Preserved fish tidbits, at age 10




144 343 4 0.4 Never 0.1-1.3

Not signif-icant


Preserved eggs Case-control (3) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Preserved eggs- not specified, but measured salted egg, fermented black egg





0.88-1.55


NAS01056

Lee

1994

Century egg, an unsalted preserved egg, at age 10




151 341 3 0.8 Never 0.4-1.6


1 June, 2006


147

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

Century egg, an unsalted preserved egg, at adulthood




200 406 4 1.0 Never 0.3-3.8


NAS01113

Zheng

1994

Salted, dried and tinned eggs




N/A N/A

Preserved fats Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Dried, salted fat






2 9.25 Not clear

3.9-21.5


Preserved plant foods Total preserved vegetables: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: Preserved vegetables

Ever vs Never



375 327 2 N/A N/A N/A Not Signif-icant


1 June, 2006


148

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

All preserved vegetables (salted mustard green/ bok choi/ stem vegetables, pickled stem vegetable/ cucumber, salted root and preserved root)

≤40 times per year to > 200 times per year

FFQ - Study-specifi


935 1032 4 1.43 ≤40 times per year

1.11-1.86

N/A 0.001 Sex, Age, Educational Level, Smoking, Exposure to smoke from heated rapeseed oil and burning coal while cooking, Occupational exposure to chemical fumes, History of chronic ear and nose condition

NAS01056

Lee

1994

Canned salted or pickled vegetables, consumption during adulthood




199 405 4 4.9 Never 1.8-12.9


NAS01113

Zheng

1994

Salted, dried, or tinned vegetables in brine




N/A N/A

Total preserved vegetables: Childhood/Infancy consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Preserved vegetables Intake for Age 10

None to >59.2 grams



89 113 4 0.9 None 0.3-2.6


NAS00531

Ward

2000

Intake for Age 3: Preserved vegetables

None to > 44.8 grams



88 103 4 0.9 None 0.3-2.4


1 June, 2006


149

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

During Weaning: Preserved vegetables

None to > 0 Dietary History question-naire


87 112 2 1.3 None 0.6-2.5


NAS00531

Ward

2000

Mother's diet during breastfeeding: Preserved vegetables

Highest vs lowest



375 327 N/A 0.6 Low-est

0.2-1/5

N/A N/A N/A

NAS01056

Lee

1994

Canned salted or pickled vegetables, at age 10




149 344 4 0.5 Never 0.1-1.4


Preserved Root Vegetables Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS06024

Huang

1997

Preserved root vegetables exposed at age of 10, cases and control were from Guangdong province



104 104 2 1.81 No 1.01– 3.33

0.045 N/A Age, Sex, No Separate Kitchen, Grapes, and dired orange, Family history of cancer

NAS06024

Huang

1997

Preserved other root vegetables

consume few to consume every week

Question-naire


104 104 3 2.42 Consume few

0.99-5.92


Preserved Cruciferous Vegetables: Adulthood consumption Case-control (2)

1 June, 2006


150

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

tang chye, a type of preserved cabbage, consumption during adulthood



Singa-pore


199 406 5 1.5 Never 0.6-3.4


NAS01056

Lee

1994

chye poh, preserved Chinese radish, consumption during adulthood



Singa-pore


200 406 4 2.8 Never 1.2-6.0


NAS01922

Ning

1990

sour cabbage, consumption 3 years prior to diagnosis





Preserved Cruciferous Vegetables: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

tang chye, a type of preserved cabbage, consumption at age 10 years

Never exposed to more than 3 times per week


Singa-pore


147 342 5 0.8 Never 0.2-2.6


NAS01056

Lee

1994

chye poh, preserved Chinese radish, consumption at age 10 years



Singa-pore


150 342 4 1.0 Never 0.4-2.1


NAS01922

Ning

1990

sour cabbage, consumption at 10 years of age





1 June, 2006


151

Preserved Green Leafy Vegetables: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994



Singa-pore



N/A Age, sex, ethnicity/ race, education, belachan, canned, salted, & pickled vegetables, vitamin C, salted soy beans, kiam chye, vitamin E

Total Preserved Vegetables: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: vegetables in brine




72 72 2 2.77 N/A 1.34-5.71


NAS00577

Yuan

2000

Preserved leafy vegetables (salted mustard green, salted bok choi, etc)





0.65-2.9


NAS00577

Yuan

2000

Preserved Stem Vegetables (salted stem vegetables and pickled stem vegetable)





1.24-2.84

N/A <0.001 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition

1 June, 2006


152

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Preserved root vegetables (salted root and preserved root)





0.7-1.53


NAS01056

Lee

1994




Singa-pore


200 406 4 2.8 Never 0.9-8.2


Total Preserved Vegetables: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

Mei chye (preserved greens and leafy vegetables), at age 10 years



Singa-pore


150 341 4 1.3 Never 0.6-2.6


Other Preserved Vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasoning: salted dried tomatoes




72 72 2 7.5 N/A 3.09-18.2


1 June, 2006


153

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

Plum vegetable (Chan Pai Mui), 3 years ago



104 104 Contin-uous

1.73 N/A 1.19-2.53


NAS00825

Chen

1997

Plum vegetable

Less than once a month to greater than once a week




1.04-6.19

N/A <0.05 Age, Sex, Area of Residence, Grape and Preserved Plum, No separate kitchen, Kitchen range without chimney

Preserved fruits Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Preserved fruits, 5 years pre-diagnosis





0.71-2.85


NAS00749

Armstrong

1998

Preserved fruits, at age 10





0.82-2.75

N/A N/A Unadjusted

Preserved citrus fruits Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


154

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Preserved orange, cases and control were from Guangdong province

Yes vs No

Question-naire


104 104 2 2.95 No 1.04-8.41

0.043 N/A Age, Sex, No separate kitchen, dried vegetables and grapes, Family history of Cancer

NAS06024

Huang

1997

Citrus fruits, preserved, exposed at age of 10, cases / control were from Guangdong province

Yes vs No

Question-naire


104 104 2 2.169 No 1.12-4.21


Preserved plums: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

preserved plum (gar ink gee)




N/A N/A

NAS00825

Chen

1997

preserved prune, 3 years ago





NAS00825

Chen

1997

preserved plum, 3 years ago





1 June, 2006


155

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

Preserved prune N/A FFQ - Study-specific


104 104 Contin-uous

2.59 N/A 1.04-8.41

N/A 0.043 Age, Sex, Area of Residence, Consumption of Plum Veg/ grape, No separate kitchen, Kitchen Range wo chimney, Family Cancer History

NAS00825

Chen

1997

Preserved Plum Less than once per month to 1-4 times per month




0.72-3.9

N/A <0.05 Age, Sex, Area of Residence, Plum Vegetable/ Grape, No separate kitchen, Kitchen Range wo Chimney

NAS01459

Yu

1989

preserved (salted) plum, 3 years prior to diagnosis




N/A

NAS01459

Yu

1989

gar ink gee preserved (salted plum),, 3 years prior to diagnosis




N/A

NAS01459

Yu

1989

chan pai mui, preserved (salted plum), unsure time of consumption




Age, sex, area of residence, salted fish, fermented fish sauce, moldy bean curd, salted shrimp paste, gar ink gee, tomatoes

NAS01459

Yu

1989

gar ink gee, preserved (salted plum), unsure time of consumption




Age, sex, area of residence, salted fish, fermented fish sauce, moldy bean curd, chan pai mui, salted shrimp paste, tomatoes

1 June, 2006


156

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01608

Yu

1986



China, Hong Kong




Preserved plums: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

preserved prune, 10 years old



104 104 Contin-uous

2.17 N/A 1.12-4.21


NAS00825

Chen

1997

preserved plum, 10 years old



104 104 Contin-uous

2.1 N/A 1.12-3.91


NAS01459

Yu

1989

preserved (salted) plum, at age 10

Rarely to daily




NAS01459

Yu

1989

gar ink gee, preserved (salted) plum, at age 10

Rarely to daily




NAS01608

Yu

1986



China, Hong Kong




1 June, 2006


157

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Preserved plums, exposed at age of 10, cases and control were from Guangdong province

Yes vs No

Question-naire


104 104 2 2.095 No 1.12-3.91


Preserved olives: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Olives in Brine




72 72 2 2.0 N/A 1.36-3.72


Preserved spice intake Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Harissa (chili peppers, dried then pickled and preserved in olive oil with garlic), at least once per week




72 72 2 5.0 No N/A <.001 N/A Age, sex, area of residence

NAS00531

Ward

2000

Adult Dietary Intake: hot chili sauce

Lowest to Highest



375 327 2 1.4 Lowest 0.9-2.1

N/A N/A Age, Sex, Ethnicity/ Race, Subjects w/ mothers question-naire, Total calories

1 June, 2006


158

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01812

Geser

1978

Households w/ NPC patients and of controls: mustard paste


China, Hong Kong


144 143 2 0.44 No 0.26-0.74

N/A N/A Age, sex

NAS01812

Geser

1978

Households w/ NPC patients and of controls: chilli sauce


China, Hong Kong


144 144 2 0.41 No 0.24-0.69

N/A N/A Age, sex

NAS01812

Geser

1978

Mustard paste N/A FFQ - Study-specific

China, Hong Kong



N/A Age, sex, Use of ancestral alters and Buddhist alters, Vinegar, Xanthozylon Seeds, Flavor Essence, Oyster Soy, Chinese Wine, Bread

4.2.1 Drying (dried foods) Dried animal foods Dried fish (excluding salted fish) Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

Dried, unsalted fish, adult




195 405 3 2.2 Never 0.8-5.4

Not signif-icant


1 June, 2006


159

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

Dried, unsalted fish, at age 10




141 337 3 0.1 Never 0.01-1.0

Signif-icant


NAS01056

Lee

1994

Dried, tiny fish, at age 10




148 345 5 0.6 never 0.02-2.1

Not signif-icant


NAS01056

Lee

1994

Dried, tiny fish, adult




190 306 5 1.1 never 0.3-3.8

Not signif-icant


NAS01056

Lee

1994

Dried, tiny fish, infancy




59 96 4 0.7 never 0.05-8.6

Not signif-icant


NAS01056

Lee

1994

Dried, tiny fish soup, during infancy




60 96 4 4.2 never 0.4-42.8

Not signif-icant


NAS01520

Yu

1988

Dried fish, age 10

Rarely to monthly



128 174 3 6.4 Rarely 1.6-26.8

Signif-icant

.04 Age, sex

NAS01520

Yu

1988

Dried fish, age 1-2

Rarely to monthly



128 174 3 2.2 Rarely 0.9-5.3

Not signif-icant

.002 Age, sex

NAS01922

Ning

1990

dried anchovy, at age 10





1 June, 2006


160

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

dried anchovy, 3 years prior to diagnosis





NAS04944

Armstrong

1978

dried fish, for breakfast among families of cases/ controls


60 150 N/A N/A N/A N/A Signig-icant

N/A Unadjusted

NAS04944

Armstrong

1978

dried fish in three main daily meals combined, among cases and controls

Unclear Recall Malaysia Chinese 210 25-81/ Mixed


N/A Age, Sex, Area of residence, Ethnicity/ Race, Socio-economic status, Lifestyle Factors

Dried seafood: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

dried oyster, during adulthood

Never to more than 3 times per month


Singa-pore


200 405 4 2.2 Never 0.6-7.3


NAS01056

Lee

1994

dried prawn, consumption during adulthood



Singa-pore


199 406 5 1.5 Never 0.5-3.6


NAS01608

Yu

1986



China, Hong Kong




1 June, 2006


161

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

dried shrimp, 3 years prior to diagnosis




N/A N/A

Dried seafood: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

prawn, dried, at age 10



Singa-pore


150 340 4 0.7 Never 0.3-1.4


NAS01056

Lee

1994

oyster, dried, at age 10



Singa-pore


151 342 4 1.1 Never 0.3-3.4


NAS01520

Yu

1988





N/A Age, sex

NAS01608

Yu

1986



China, Hong Kong




NAS01922

Ning

1990





N/A N/A

1 June, 2006


162

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990





N/A N/A

Dried plant foods Dried vegetables: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

Dried vegetable, consumption 3 years prior to diagnosis





Dried vegetables: Childhood/Infancy consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

Dried vegetable, consumption at 10 years of age





Dried Green Leafy Vegetables: Adulthood consumption Case-control (1)

1 June, 2006


163

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

dried kelp, 3 years prior to diagnosis





NAS01922

Ning

1990

dried seaweed, 3 years prior to diagnosis





Dried Green Leafy Vegetables: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

dried kelp, at 10 years of age





NAS01922

Ning

1990

dried seaweed at 10 years of age





Dried plums: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00577

Yuan

2000

Dried plum (chan pai mui)




N/A N/A

1 June, 2006


164

Dried plums: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

various dried plums, at age 10




N/A Age, sex

Dried olives: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Dried Olives




72 72 2 4.66 N/A 1.51-14.33


Other dried fruits: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Raisins Currently- twenty years ago



72 72 2 0.2 N/A 0.08-0.17


NAS00577

Yuan

2000

dried red date (gone hong zhao)




N/A N/A

1 June, 2006


165

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01608

Yu

1986



China, Hong Kong




NAS01608

Yu

1986

dried fruits (chan pai mui, gar ink gee), at 10 years of age or 3 years prior to diagnosis


China, Hong Kong




Other dried fruits: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

dried red date, at age 10




N/A Age, sex

NAS01608

Yu

1986



China, Hong Kong




Dried seeds: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool




No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00577

Yuan

2000

dried ginko seed (bei guo)




N/A N/A

1 June, 2006


166

Dried seeds: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool




No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

dried gingko seed, consumed by subject at age 10




N/A Age, sex

Dried spice intake Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Dried Peppers




72 72 2 5.5 N/A 2.55-11.8


4.2.2 Storage Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Foods for chewing when teething: cherchem (wheat or barley pieces that have softened through contact w/ the floor and walls when these cereals are stored underground)

Ever vs Never


Algeria Un-known

144 9-70/ Mixed

72 72 2 4.0 Ever 0.18-4.4


1 June, 2006


167

4.2.3 Bottling, canning, vacuum packing Case-control (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01812

Geser

1978

Households of NPC patients / controls: Tinned food w/ fish


China, Hong Kong


150 150 2 0.46 No 0.23-0.94

N/A N/A Age, sex

4.2.5.1 Salt Case-control (2) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01459

Yu

1989

Table salt use, 3 years prior to diagnosis





NAS01459

Yu

1989

Table salt use, at age 10





NAS01520

Yu

1988

Table salt use, at age 10




N/A Age, sex

4.2.5.3 Salted foods Salted composite foods Case-control (1)

1 June, 2006


168

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04928

Henderson

1976

Salted snacks

Yes vs. no Interview United States


156 267 2 0.4 No N/A 0.03 N/A Age, race, area of residence, ethnicity/ race

4.2.5.3.1 Salted animal food Salted meat: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990





N/A N/A

Salted meat: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

salted meat, at age 10




N/A N/A

Salted pork Case-control (3)

1 June, 2006


169

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01190

Zheng

1993

Salted pork N/A FFQ - Study-specific

China Chinese 410 N/A./ Mixed


N/A Un-adjusted

NAS01520

Yu

1988

Salted pork, at age 10




N/A Age, sex

NAS01608

Yu

1986

Salted pork, at age 10 or adult





Salted fish: Adulthood consumption Cohort (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Chi-square

Ref group

CI P value

p value for trend

Adjusted for

NAS06011

Zou

1994

Salted fish, 1960s





Not exposed


NAS06011

Zou

1994

Salted fish, 1970s





Not exposed


NAS06011

Zou

1994

Salted fish, 1980s





Not exposed

N/A .214 N/A Unadjusted

Case-control (21) Meta-analysis

1 June, 2006


170

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS00531

Ward

2000

Salted fish, adult intake

5g/wk Dietary History question-naire

China, Taiwan


375 327 2 0.8 No 0.5-1.2

Not signif-icant


NAS00577

Yuan

2000

Salted fish Less than monthly to weekly or more




0.86-3.88

N/A 0.07 Age, sex, area of residence, env factors, smoking, chemical fumes, history of ear/nose condition

NAS00749

Armstrong

1998

Salted fish, 5 years prior





2.23-7.99

Signif-icant

.001 Unadjusted

NAS01056

Lee

1994

Salted fish, adult




200 406 4 4.4 Never 0.7-25.9

Not signif-icant


NAS01113

Zheng

1994

Salted fish, year before dx




N/A Age, sex, area of residence, SES

NAS01141

Zheng

1994

Salted fish, tough meat





4.6-32.0

Signif-icant


NAS01141

Zheng

1994

Salted fish, soft meat





4.1-152

Signif-icant


1 June, 2006


171

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS01153

West

1993

Salted fish Low to high tertile


104 101 3 1.3 Low tertile 0.69-2.6

Not signif-icant

N/A Age, sex, fresh fish, processed meat, hospital ward

NAS01190

Zheng

1993





N/A N/A

NAS01248

Sriamporn

1992

Salted fish Freshwater only, sea salted +/- once a week



120 120 3 2.5 Fresh-water only

1.2-5.2

Signif-icant

N/A Age, sex, area of residence, smoking, alcohol, occupation

NAS01459

Yu

1989

Salted fish, 3 years prior to dx

Rarely to daily



306 306 4 1.8 Rarely 0.9-3.6

Not signif-icant


NAS01608

Yu

1986

Salted fish, adult

Rarely to daily


China, Hong Kong


250 250 4 7.5 Rarely 0.9-65.3

Not signif-icant

N/A Age, sex

NAS01608

Yu

1986

Salted fish head soup, adult



China, Hong Kong


250 250 2 4.2 Rarely 1.6-11.7

Signif-icant

N/A Age, sex

NAS01922

Ning

1990

salted fish, ever consumed

Ever vs. Never



100 300 2 2.2 Never 1.3-3.7


1 June, 2006


172

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS01922

Ning

1990

Salted fish age at first exposure

Never exposed to older than 21



100 300 4 1.5 Never 0.7-3.3


NAS01922

Ning

1990

salted fish, duration of consumption (years)

Never exposed to more than 21 years



100 300 4 2.8 Never 1.4-5.6


NAS01922

Ning

1990

2.5.2 salted fish, 3 years prior to diagnosis





0.41 Age, Sex, Area of residence

NAS01922

Ning

1990

salted fish, age/ duration at first exposure

Never exposed to age 21+/ duration 11+ years




NAS01922

Ning

1990

salted fish, age/ duration at first exposure (those who consumed at least monthly during the earliest decade of exposure)

Never exposed to 11+ years at first exposure and 11+ years duration




NAS02182

Armstrong

1983

Salted fish, current consumption as adults

N/A N/A Malaysia Chinese 200 N/A/

Mixed


N/A Age, Sex, Area of residence, Ethnicity/ Race

1 June, 2006


173

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS04928

Henderson

1976

Current use of salted fish

N/A N/A United States



N/A Age, Sex, Area of residence, SES

NAS05679

Yang

2005

Salted fish, moldy and firm, after age 10





NAS06003

Ye

1995

salted fish ≤ 4 time per month to > 4 times per month



135 135 2 5.0 ≤ 4 time per month

1.26- 19.6


NAS60010

Cai

1996

Salted Fish <12 times per month to ≥12 times per month



115 115 2 1.318 < 12 times per month

0.995-1.793


NAS06021

Chen

1994

Salted Fish frequently consumed

Question-naire


28 28 Contin-uous

r2= 0.8661

N/A N/A 0.008 N/A Sex, Age

NAS06021

Chen

1994

Salted Fish, frequently consumed

Yes or No Question-naire


28 28 2 5.51 No 1.74-17.46

<0.01 N/A Sex, Age

1 June, 2006


174

Study identifier

Author

Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


Adjusted for

NAS06022

Wang

1993

Salted Fish, consumed frequently

less consumed to frequently consumed

Question-naire


122 122 2 8.99 less consumed

N/A 0.0127 N/A Consumption of pork fat, colored vegetables, whole grains, plant oils, and vegetables, Non-nutrient chemicals, smoking in living area, Sex, Age, SES

NAS06023

Zou

1999

Salted Fish < 9 times a month to ≥ 9 times a month

Question-naire


100 202 2 2.8 < 9 times a month

1.52-5.18

Significant N/A Age, Sex, Live in area with high level of background radiation, Alcohol, Smoking habits, Consumption of fermented soy


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Categories

RR/OR Ref group


Ad-justed for

NAS01222

Zou

1992

Nitrosamines from salted fish

36.96-183.85 ug/kg

Food testing

China Chinese N/A N/A/ Mixed

21 N/A Mean exposure: cases v. controls

N/A N/A N/A No tests of signif-icance

N/A N/A

Salted fish: Childhood consumption (Age 10) Cohort (1)

1 June, 2006


175

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Chi-square

Ref group

CI P value

p value for trend

Adjusted for

NAS06011

Zou

1994

Salted fish, childhood





Not exposed



Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS00531

Ward

2000



China, Taiwan


82 110 2 1.5 No 0.8-2.8

Not signif-icant


NAS00749

Armstrong

1998






1.59-4.75

Signif-icant

N/A Unadjusted

NAS00821

Hildesheim

1997

Salted fish during childhood

Yes or no Unknown China, Taiwan


364 320 2 1.4 No 0.47-4.5

Not signif-icant

N/A Age, sex

NAS01056

Lee

1994





161 369 5 0.8 Never 0.2-2.9

Not signif-icant


NAS01113

Zheng

1994






NAS01113

Zheng

1994

Salted fish soup, age 2-10





1 June, 2006


176

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01141

Zheng

1994

Salted fish, tough meat, age 10





5.1-16.4

Signif-icant


NAS01141

Zheng

1994

Salted fish, soft meat, age 10





5.2-20.7

Signif-icant


NAS01190

Zheng

1993





N/A N/A

NAS01459

Yu

1989


Rarely to daily



306 306 4 2.1 Rarely 1.2-3.6

Signif-icant


NAS01520

Yu

1988

Salted fish, age 10

Rarely to monthly



128 174 3 1.5 Rarely 0.5-4.3

Not signif-icant

N/A Age, sex

NAS01520

Yu

1988





N/A Age, sex

NAS01608

Yu

1986

Salted fish, age 10

Rarely to more than weekly


China, Hong Kong


250 250 3 37.7 Rarely 14.1-100

Signif-icant

N/A Age, sex

NAS01608

Yu

1986




China, Hong Kong


250 250 2 5.1 Rarely 2.6-10.4

Signif-icant

N/A Age, sex

1 June, 2006


177

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01712

Armstrong

1983

Salted fish, child Ever v. never


100 100 2 17.4 Never 2.7-111

Signif-icant


NAS01766

Lanier

1980

Salted fish, child Yes or no Question-naire

United States, Alaska

Alaskan native

26 32-80/ Mixed

13 13 2 4.0 No 0.4-19.7

Not signif-icant

N/A Age, sex, area of residence, ethnicity/ race

NAS01922

Ning

1990

salted fish, at age 10 years




100 300 4 6.7 Never N/A N/A 0.003 Age, Sex, Area of residence, salted shrimp paste and carrot consumption at 10 years

NAS01922

Ning

1990


Ever vs Never



100 300 2 4.2 Never 2.2-8.3


NAS01922

Ning

1990


Ever vs Never



100 300 2 1.6 Never 0.8-3.2


NAS02182

Armstrong

1983


Ever vs Never


Mixed

100 100 2 3.0 Never N/A 0.04 N/A Age, Sex, Area of residence, Ethnicity/ Race

NAS02182

Armstrong

1983


Never to daily


Mixed

100 100 3 17.4 Never 2.7-111.1


1 June, 2006


178

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS02182

Armstrong

1983

NPC and Salted Fish, Consumption during adolescence



Mixed


1.2- 10.7


NAS05679

Yang

2005

Salted fish, moldy and firm, during childhood

Never vs. 1+ times/wk



502 1942 3 1.78 Never 0.82-3.89

Not signif-icant


NAS06020

Na

1988


N/A Question-naire


127 217 Contin-uous

r2= 1.575


N/A Area of residence, coal as family fuel, History of cancer/ naso-pharyngitis, Sex, Age

NAS06020

Na

1988


consume less to more

Question-naire


127 217 2 5.5 Consume less

1.16-35.89


Salted fish: Childhood consumption (Ages 0-3) Case-control (10) Meta-analysis Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS00531

Ward

2000



China, Taiwan


86 102 2 1.0 No 0.5-2.1

Not signif-icant


NAS01056

Lee

1994

Salted fish, during infancy




200 406 3 1.2 Never 0.3-3.4

Not signif-icant

N/A Age, sex, ethnicity/ race, education

1 June, 2006


179

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01113

Zheng

1994





NAS01113

Zheng

1994






NAS01113

Zheng

1994

Salted fish soup, before 2





NAS01141

Zheng

1994






5.2-20.6

Signif-icant


NAS01190

Zheng

1993





N/A N/A

NAS01381

Jeannel

1990

Salted anchovies, during weaning




NAS01459

Yu

1989


Rarely to weekly



306 306 3 2.0 Rarely 1.1-3.6

Signif-icant


NAS01459

Yu

1989




306 306 2 2.1 No 1.2-3.6

Signif-icant


1 June, 2006


180

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01520

Yu

1988


Rarely to monthly



128 174 3 2.2 Rarely 0.7-7.6

Not signif-icant

.11 Age, sex

NAS01520

Yu

1988




128 174 2 2.6 No 1.2-5.6

.01 N/A Age, sex

NAS01608

Yu

1986

Salted fish, age 1-2 by mother

Never to often


China, Hong Kong


250 250 3 20.2 Never 6.8-60.2

Signif-icant

N/A Age, sex

NAS01608

Yu

1986

Salted fish, during weaning (mother)

Ever v. never


China, Hong Kong


250 250 3 7.5 Never 3.9-14.8

Signif-icant

N/A Age, sex

NAS01608

Yu

1986

Salted fish head soup, age 1-2 (mother)

Ever v. never


China, Hong Kong


250 250 2 8.3 Never 2.5-32.5

Signif-icant

N/A Age, sex

NAS01812

Geser

1978

Salted fish, after weaning


China, Hong Kong


150 150 2 2.6 No N/A < 0.01 N/A Unadjusted

NAS01812

Geser

1978

Salted Fish During Weaning

No salted fish / low traditional life-style index to yes salted fish/ high traditional lifestyle index


China, Hong Kong


98 89 6 2.2 No salted fish and low traditional life-style index


N/A traditional lifestyle: compilation of Chinese wine drinking, bread consumption, ancestral / Buddhist alters

1 June, 2006


181

Salted fish: Mother’s consumption during pregnancy or breastfeeding Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

Salted fish, during breast-feeding




49 96 3 2.0 never 0.3-10.6

Not signif-icant


NAS01056

Lee

1994





46 94 3 1.3 never 0.4-3.7

Not signif-icant


NAS01459

Yu

1989

Salted fish, during nursing

Rarely to daily



306 306 4 2.3 Rarely 1.1-4.6

Signif-icant


NAS01459

Yu

1989


Rarely to daily



306 306 4 2.2 Rarely 1.1-4.6

Signif-icant


NAS01520

Yu

1988

Salted fish, while nursing

Rarely to monthly



128 174 3 4.9 Rarely 1.5-15.9

Signif-icant

.01 Age, sex

NAS01520

Yu

1988


Rarely to monthly



128 174 3 3.1 Rarely 1.1-8.8

Signif-icant

.003 Age, sex

Salted seafood: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


182

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Salted seafood pastes

Yes vs. no



935 1032 2 1.44 No 0.97-2.15

0.07 N/A Age, sex, occupational exposure to fumes, education, smoking, environmental factors, other diseases

NAS01459

Yu

1989





N/A N/A

NAS01459

Yu

1989

salted shrimp paste, unsure time of consumption




N/A Area of residence, age, sex, salted fish, fermented fish sauce, moldy bean curd, chan pai mui, gar ink gee, tomatoes

NAS01922

Ning

1990


Never to Weekly



100 300 3 1.8 Never 0.9-3.8


Salted seafood: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

salted shrimp paste, during ages 1-2

Rarely to weekly




NAS01459

Yu

1989

salted shrimp paste, at age 10

Rarely to daily




1 June, 2006


183

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

salted shrimp paste, at 10 years

None to weekly/ daily



100 300 4 3.2 None N/A 0.007 N/A Age, Sex, Area of residence, salted fish and carrot consumption at 10 years

Salted eggs: Adulthood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: salted eggs

Lowest to highest



89 113 2 2.0 N/A 1.2-3.2

N/A N/A Age, Sex, Ethnicity/ Race, Total calories, Subjects w/ mothers questionnaire

NAS00749

Armstrong

1998

Salted eggs, 5 years pre-diagnosis




282 282 3 2.55 Monthly 1.44-4.53


NAS00749

Armstrong

1998







NAS01056

Lee

1994

Salted egg, during adulthood




200 406 4 1.4 Never 0.6-3.2


1 June, 2006


184

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

salted chicken or duck egg, 3 years prior to diagnosis




N/A N/A

NAS04944

Armstrong

1978

salted egg in three main daily meals combined, among cases and controls




Salted eggs: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Salted eggs, consumption at age 10




282 282 3 2.4 Monthly 1.4-4.11

N/A N/A Unadjusted

NAS00749

Armstrong

1998







NAS01056

Lee

1994

salted egg, at age 10




149 344 4 0.5 Never 0.2-1.5


1 June, 2006


185

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01520

Yu

1988

salted duck eggs, during weaning



128 174 2 5.0 No 1.2-21

0.06 N/A Age, sex

NAS01922

Ning

1990

salted chicken or duck egg, at age 10




N/A N/A

4.2.5.3.2 Salted plant food Salted vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01190

Zheng

1993

Salted vegetables N/A FFQ - Study-specific


205 205 N/A N/A N/A N/A Signif- icant

N/A N/A

NAS01922

Ning

1990

Salted vegetable, consumption 3 years prior to diagnosis





Salted vegetables: Childhood/Infancy consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

1 June, 2006


186

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

Salted vegetable, consumption at 10 years of age





Salted Root Vegetables Case-control (1) Study identifier

Author, Yr

Exposure Exposure range Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06023

Zou

1999

Salted root vegetables

< 9 times a month to ≥ 9 times a month

Question-naire


97 192 2 2.2 < 9 times a month

1.3-3.6


Salted Cruciferous Vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

kiam chye, salted mustard greens, consumption during adulthood



Singa-pore


200 406 4 3.1 Never 1.4-6.5


NAS01608

Yu

1986

salted mustard green (mui choi), subject's consumption at 10 years of age or 3 years prior to diagnosis





Salted Cruciferous Vegetables: Childhood consumption Case-control (2)

1 June, 2006


187

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

kiam chye, salted mustard greens, consumption at 10 years old



Singa-pore


148 344 4 1.1 Never 0.4-2.6


NAS01520

Yu

1988

salted mustard greens, consumed by subject during weaning



128 174 2 5.4 No 1.2-23.8

0.06 N/A Age, sex

NAS01520

Yu

1988

salted mustard green, consumed by subject between ages 1 to 2 years

Rarely to weekly



128 174 3 1.6 Rarely 0.5-4.7

0.06 N/A Age, sex

NAS01520

Yu

1988

salted mustard green, consumed by subject at age 10

Rarely to weekly



128 174 3 1.3 Rarely 0.3-6.7

Not signif-icant

Not signif-icant

Age, sex

NAS01520

Yu

1988

salted cabbage, consumed by subject at age 10




N/A Age, sex

NAS01520

Yu

1988

salted radish, consumed by subject at age 10




N/A Age, sex

NAS01520

Yu

1988

salted mustard green, consumed by subject during weaning

Rarely to monthly




N/A Age, sex

Salted Green Leafy Vegetables: Adulthood consumption Case-control (1)

1 June, 2006


188

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Salted green leafy vegetables, 5 years pre-dx




282 282 3 3.33 Monthly 1.84-6.01


Salted Green Leafy Vegetables: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

Salted green leafy vegetables, at age 10




282 282 3 0.84 Monthly 0.45-1.58

N/A N/A Unadjusted

Salted Vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00825

Chen

1997

Salted vegetables, 3 years ago



104 104 N/A N/A N/A N/A Not signfi- icant


NAS06023

Zou

1999

Salted other non-starchy vegetables

None to ≥ 9 times a month

Question-naire


100 202 4 2.28 None 1.4-3.73


Salted Vegetables: Childhood consumption Case-control (2)

1 June, 2006


189

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

salted vegetables, 10 years old



104 104 Contin-uous

0.76 N/A 0.58-0.99


NAS06024

Huang

1997

Salted vegetables, exposed at age of 10, cases /control were from Guangdong province



104 104 2 0.755 No 0.58-1.0


Other Salted Vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998

salted root, 5 years pre-diagnosis




282 282 3 2.19 monthly 1.33-3.62


NAS01056

Lee

1994

sze chuan chye, a salted Chinese tuber, consumption during adulthood



Singa-pore


197 404 4 2.4 Never 1.1-5.2


Other Salted Vegetables: Childhood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


190

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00749

Armstrong

1998





282 282 3 1.75 monthly 0.98-3.10

N/A N/A Unadjusted

NAS01056

Lee

1994

sze chuan chye, a salted Chinese tuber, consumption at age 10 years



Singa-pore


145 340 4 1.4 Never 0.4-4.5


NAS01520

Yu

1988


Rarely to daily



128 174 4 3.2 Rarely 0.6-17.6

0.03 (one sided)

N/A Age, sex

NAS01520

Yu

1988

chung choi, consumed by subject during weaning



128 174 Contin-uous

0.518 N/A N/A 0.021 (one sided)

N/A Age, sex, other household member smoked at birth, salted fish during pregnancy, salted duck egg/ salted mustard green during weaning, dried fish/ fermented soy paste during ages 1 and 2 yr

Salted olives: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

salted black olives, during adulthood



Singa-pore


200 406 3 1.6 Never 0.3-7.5


Salted olives: Childhood consumption

1 June, 2006


191


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

salted black olives, at age 10



Singa-pore


151 344 3 0.3 Never 0.1-0.9


NAS01520

Yu

1988

salted olive, at age 10




N/A Age, sex

Salted soy: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

salted soy beans, during adulthood

Never exposed to > 3 times per week



199 406 5 6.7 Never 1.2-36.6


NAS01190

Zheng

1993

Salted Soya Bean Pastes


China Chinese 410 N/A. Mixed


N/A N/A

Salted soy: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


192

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

salted soy beans, at age 10 year

Never exposed to 1-3 times a week



146 342 4 1.1 Never 0.5-2.2


Other salted pulses/legumes Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

salted black beans, consumption during adulthood

Never exposed to > 3 times per month



200 406 4 2.1 Never 0.8-5.4


NAS01056

Lee

1994

salted black beans, consumption at age 10 years

Never exposed to more than three times per month



148 341 4 1.0 Never 0.4-2.,3


4.2.6 Pickling (pickled foods) Total pickled foods Case-control (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories


p value for trend

Adjusted for

NAS06030

Huang

2002

Pickled foods

Less to frequently consumed

Questionnaire China Chinese 525 10-78/ Mixed


1.706-5.707


1 June, 2006


193

Pickled vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

Pickled vegetable, 3 years prior to diagnosis





NAS06002

Duan

2000

Pickled vegetables

N/A Question-naire


100 100 Continuous r2 = 0.015


N/A Environmental Factors, Gas Range, Pungent foods, SES

Pickled vegetables: Childhood/Infancy consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01381

Jeannel

1990

Dietary Intake During Weaning: Consumption of Pickled Vegetables

Less than once a month to more than 2 a week




N/A N/A N/A Age, Sex, Area of Residence, Living condition score

NAS01922

Ning

1990

Pickled vegetable, at age 10





Pickled Root Vegetables Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


194

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06024

Huang

1997

Pickled root vegetables, exposed at age of 10, cases /control were from Guangdong province



104 104 2 0.75 No 0.57-0.99


Pickled Cruciferous Vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr

Exposure Exposure range Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00825

Chen

1997

Pickled chinese cabbage, 3 years ago





NAS06003

Ye

1995

Pickled leaf mustard

Less than 4.2 times per month to greater than 75 times per month



135 135 3 6.11 ≤ 4 .2 times per month

N/A < 0.01 N/A Age, Sex, Area of residence

NAS06003

Ye

1995

pickled radish <75 times per month to ≥ 75 times per month



135 135 2 1.75 ≤ 75 times per month

1.1-2.79


Pickled Cruciferous Vegetables: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

1 June, 2006


195

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00825

Chen

1997

Pickled Chinese Cabbage, 10 years old



104 104 Continuous 0.75 N/A 0.57-0.99


NAS01520

Yu

1988

pickled cabbage, consumed by subject at age 10




N/A Age, sex

Other Pickled Vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01381

Jeannel

1990

Intake During Preceding Year to Diagnosis: Fungus on Pickled Vegetables




NAS06023

Zou

1999

pickles <9 times/ month to ≥ 9 times/ month




1.3-3.6


Other Pickled Vegetables: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


196

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01381

Jeannel

1990

During Weaning: Fungus on pickled vegetables




Pickled olives: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01381

Jeannel

1990

During Preceding Year to Diagnosis: Pickled Olives

Less than once a month to > 8 times / month




N/A N/A N/A Age, sex, area of residence, living condition score

NAS01381

Jeannel

1990

Preceding Year to Diagnosis: Pickled Olives

<once/ month to > 8 times / month




N/A N/A N/A Age, sex, area of residence

Pickled spice intake Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00424

Laouamri

2001

Seasonings: Pickled Peppers




72 72 2 2.85 N/A 1.25-6.45


1 June, 2006


197

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04944

Armstrong

1978

pickled chili, in three main daily meals combined, among cases and controls


60 150 2 0.3 N/A N/A <.01 N/A Age, sex, ethnicity/ race,SES, household type, area of residence

4.2.7.1.1 Cured meats Cured meat: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: cured meats

Never vs. Ever


China, Taiwan




NAS01922

Ning

1990

cured meat, 3 years prior to diagnosis




N/A N/A

Cured meat: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00531

Ward

2000



China, Taiwan


89 111 2 1.11 No 0.6-2


1 June, 2006


198

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00531

Ward

2000



China, Taiwan


92 109 2 0.8 No 0.4-1.8


NAS01922

Ning

1990

cured meat, at age 10




N/A N/A

4.2.7.1.2 Smoked foods Smoked meat: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: smoked meats

Never vs. Ever


China, Taiwan




NAS00544

Chelleng

2000

smoked meat Never & rarely to frequently

Unknown-NA

India Indian 141 Mean 44/ Mixed

47 94 2 10.8 Never & rarely

3.4-39

0.0002 N/A Age, sex, ethnicity/ race, Area of residence, Alcohol / Smoking / betel nut chewing habits, type of house, number of windows, kitchen inside/ outside, soot in living room, type of cooking fuel, smokeless tobacco use

1 June, 2006


199

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

smoked meat, consumption 3 years prior to diagnosis




N/A N/A

NAS06023

Zou

1999




102 202 2 1.8 No 1.09-2.97

0.02 N/A Unadjusted

Smoked meat: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00531

Ward

2000

Smoked meat, Age 10


China, Taiwan


92 114 2 1.1 No 0.5-2.4


NAS00531

Ward

2000

Smoked meat, at Age 3


China, Taiwan


92 110 2 1.2 No 0.4-3.3


NAS00531

Ward

2000

Smoked meat, During Weaning


China, Taiwan


89 112 2 2.2 No 0.2-27.6


NAS01922

Ning

1990

smoked meat, at age 10




N/A N/A

4.3 Processing

1 June, 2006


200

Processed meat: Adulthood consumption Case-control (5) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00700

Farrow

1998

Processed, preserved meat (ham, bacon, sausage, liverwurst, hot dogs)

Lowest to highest

FFQ – Block

United States


129 204 4 1.54 Lowest 0.71-3.33


NAS01056

Lee

1994

lapcheong, Chinese sausage, during adulthood



Singa-pore


200 406 4 1.0 Never 0.3-2.8


NAS01153

West

1993

Processed meat, including ham and longanisa

Low to high tertile

Unknown Philip-pines

Filipino 205 11-83/ Mixed

104 205 3 0.46 Low tertile

0.2-1.0

N/A N/A Age, sex, fresh fish, processed meat, hospital ward, Smoking, Burning anti-mosquito coils. Dust/ exhaust, Formaldehyde, Herbal medicines, Education

NAS01608

Yu

1986






NAS06023

Zou

1999




102 202 2 1.8 No 1.09-2.97

0.02 N/A Unadjusted

Processed meat: Childhood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

1 June, 2006


201

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01056

Lee

1994

lapcheong, Chinese sausage, at age 10



Singa-pore


149 344 4 0.8 Never 0.3-2.4


NAS01520

Yu

1988





N/A Age, sex

NAS01608

Yu

1986







Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01520

Yu

1988

Ham, at age 10




N/A Age, sex

NAS01520

Yu

1988





N/A Age, sex

NAS01608

Yu

1986






1 June, 2006


202

4.3.1 Refining Bread: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01459

Yu

1989

Bread, consumption at age 3 years prior to diagnosis





NAS01812

Geser

1978

Bread eaten often, by household of cases and controls



147 147 2 0.43 No 0.27-0.7

N/A N/A Age, Sex

NAS04944

Armstrong

1978

Bread, for breakfast among families of participants


60 150 N/A OR > 1


N/A Unadjusted

Bread: Childhood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00424

Laouamri

2001

Foods for chewing when teething: crust of bread

Ever vs Never


Algeria Un-known

144 9-70/ Mixed

72 72 2 OR = 1

Ever N/A N/A N/A Age, Sex, Area of residence

NAS01459

Yu

1989

Bread, consumption at age 10





1 June, 2006


203

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

Bread, consumed by subject at age 10




N/A Age, Sex

Noodles Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04944

Armstrong

1978

Noodles in three main daily meals combined, among cases and controls



N/A Ethnicity/ Race, Census district, Household type, Socio-economic status, Sex, Age

Rice Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04944

Armstrong

1978

Rice, for breakfast; families of participants


60 150 N/A OR > 1


N/A Unadjusted

NAS04944

Armstrong

1978

Plain rice, at evening meal; families of participants


60 150 N/A OR < 1


N/A Unadjusted

1 June, 2006


204

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Cont-rols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS04944

Armstrong

1978

Rice porridge, at evening meal among families of participants


60 150 N/A OR > 1


N/A Unadjusted

NAS06024

Huang

1997

Rice, exposed at age 10, specific on rice cases and control were from Heilongjiang province



104 104 2 0.707 No 0.505-0.92



Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

r2 Ref group

CI P value

p value for trend

Adjusted for

NAS00817

Koo

1997


Food survey

China, Hong Kong

Chinese N/A Male N/A N/A Continuous 0.86 N/A N/A .001 N/A age

NAS00817

Koo

1997


Food survey

China, Hong Kong

Chinese N/A Female N/A N/A Continuous 0.85 N/A N/A .034 N/A age

4.3.2 Hydrogenation Margarine Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


205

Study identifier

Author, Yr


Assess-ment

Tool

Coun-try Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

margarine, at age 10

Never to >3 times a week



113 340 5 0.6 Never 0.3-1.1


4.3.3 Fermenting Fermented soy/tofu: Adulthood consumption Case-control (6) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: fermented soybean products

Never vs. ever


China, Taiwan




NAS00577

Yuan

2000

Fermented beans/ pastes (not specified, but measured fermented bean curd (fu yu), fermented bean paste (tau ban cheung)





1.39-2.22

N/A <0.001 Sex, Age, Educational Level, Smoking, Exposure to smoke from heated rapeseed oil and burning coal while cooking, Occupational exposure to chemical fumes, History of chronic ear and nose condition

NAS01459

Yu

1989

moldy bean curd, 3 years prior to diagnosis





1 June, 2006


206

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

moldy bean curd, unsure time of consumption




N/A Age, sex, area of residence, salted fish, fermented fish sauce, salted shrimp paste, chan pai mui, gar ink gee, tomatoes

NAS01608

Yu

1986






NAS01922

Ning

1990

moldy bean curd, preserved, 3 years prior to diagnosis





NAS01922

Ning

1990

smelly bean curd, consumption 3 years prior to diagnosis





NAS01922

Ning

1990

fermented soy/flour paste, consumption 3 years prior to diagnosis





NAS06023

Zou

1999

Fermented soy < 9 times a month to ≥ 9 times a month



100 202 2 1.45 < 9 times a month

0.78-2.83

N/A N/A Age, Sex, Live in area with high level of background radiation, Alcohol, Smoking habits, Salted fish

NAS06023

Zou

1999

tofu, soy products

Never to ≥ 9 times a month



102 201 2 2.36 Never 0.26-21.3

0.17 N/A Unadjusted

Fermented soy/tofu: Childhood consumption

1 June, 2006


207


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

2.3 Fermented soybean products, at Age 10

< 16 grams to ≥ 118.8 grams


China, Taiwan


98 115 4 0.5 < 16 grams

0.2-1.2


NAS00531

Ward

2000

Fermented soybean products, at Age 3

None to ≥80.4 grams


China, Taiwan


93 111 4 0.7 None 0.3-1.9


NAS00531

Ward

2000

During Weaning Fermented soybean products

None to 12.04 grams


China, Taiwan


90 113 4 0.6 None 0.3-1.3


NAS01056

Lee

1994

fermented bean curd, at age 10




151 341 4 0.8 Never 0.4-1.8


NAS01459

Yu

1989

Moldy bean curd, ages 1-2

Rarely to weekly




NAS01459

Yu

1989

Moldy bean curd, at age 10

Rarely to daily




NAS01520

Yu

1988

fermented soy bean paste, ages 1 to 2

Rarely to weekly



128 174 3 3.6 Rarely 1.6-8.1

N/A 0.007 Age, sex

NAS01520

Yu

1988

fermented soy bean paste, at age 10

Rarely to weekly



128 174 3 1.5 Rarely 0.8-3.0


Age, sex

1 June, 2006


208

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01520

Yu

1988

moldy bean curd, consumed at age 10




N/A Age, sex

NAS01520

Yu

1988


Rarely to monthly



128 174 Contin-uous

r2 = -.23


NAS01520

Yu

1988


Rarely to weekly



128 174 Contin-uous

r2 = .988


NAS01608

Yu

1986






NAS01922

Ning

1990

moldy bean curd, preserved, at age 10





NAS01922

Ning

1990

smelly bean curd, consumption at 10 years of age





1 June, 2006


209

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01922

Ning

1990

fermented soy/flour paste, consumption at 10 years of age





Other fermented pulses/legumes Cohort (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

RR Ref group

CI P value

p value for trend

Adjusted for

NAS06046

Lin

1997

Fermented pulses

<2 times a week- 6+ times a week

Question-naire

China, Taiwan



2.2-72.3



Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01520

Yu

1988

fermented black bean paste, consumed by subject between ages 1 to 2 years

Rarely to weekly



128 174 3 4.6 Rarely 1.8-11.4

N/A 0.0009 Age, sex

NAS01520

Yu

1988

fermented black bean paste, consumed by subject at age 10

Rarely to weekly



128 174 3 1.4 Rarely 0.6-3.1


Age, sex

NAS06023

Zou

1999

Fermented beans <9 times/ month to ≥9 times/ month




1.3-3.4


1 June, 2006


210

Fermented fish Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01459

Yu

1989

Fermented fish sauce -adult





NAS01459

Yu

1989

Fermented fish sauce -age 10

Rarely to daily




NAS01459

Yu

1989

Fermented fish sauce -age 1-2

Rarely to weekly




NAS01520

Yu

1988

Fermented fish paste, age 10




N/A Age, sex

Fermented seafood: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

fermented crab paste, at age 10




N/A Age, sex

NAS01520

Yu

1988

fermented shrimp paste, at age 10




N/A Age, sex

1 June, 2006


211

Fermented eggs Case-control (2) Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

pay dann - a kind of fermented duck egg, at age 10

Rarely to weekly




N/A Age, sex

NAS01922

Ning

1990

fermented duck egg, at 10 years of age




N/A N/A

NAS01922

Ning

1990

fermented duck egg, 3 years prior to diagnosis




N/A N/A

Soy sauce: Adulthood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Soy sauce (see yao)




N/A N/A

NAS01813

Shanmugaratnam

1978

Soya Sauce (Ear, Nose, and Throat Department controls)






1 June, 2006


212

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01813

Shanmugaratnam

1978

Soya Sauce (Non-ENT hospital controls)






NAS04944

Armstrong

1978

thin soya sauce, in three main daily meals combined, among cases and controls



N/A Age, sex, ethnicity/ race,SES, household type, area of residence

NAS04944

Armstrong

1978

thin soya sauce, for breakfast among families of participants



N/A N/A

Other fermented condiment intake: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Fish sauce (yu lo)




N/A N/A

NAS00577

Yuan

2000

Oyster sauce (ho yao)




N/A N/A

NAS01812

Geser

1978

Oyster Soy


China, Hong Kong



N/A Age, sex, Use of ancestral alters and Buddhist alters, Vinegar, Xanthozylon Seeds, Flavor Essence, Mustard Paste, Chinese Wine, Bread

1 June, 2006


213

Other fermented condiment intake: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01520

Yu

1988

soy sauce, at age 10




N/A N/A

NAS01520

Yu

1988

fish sauce, at age 10




N/A N/A

NAS01520

Yu

1988

oyster sauce, at age 10




N/A N/A

4.3.5.1 Flavours Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01113

Zheng

1994

Monosodium glutamate, in the year before diagnosis

Yes or No




NAS01812

Geser

1978

Flavour Essence

Yes vs No



147 147 2 N/A No N/A Not Signif-icant

N/A Age, Sex, lifestyle factors, Vinegar, Xanthozylon Seeds, Oyster Soy, Mustard Paste, Chinese Wine, Bread

1 June, 2006


214

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS06002

Duan

2000

pungent foods N/A Question-naire


100 100 Continuous r2 = -1.695


N/A Environmental Factors, Pickled foods, SES

4.3.5.4.1 Nitrites and nitrates (as food additives) Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Intake: nitrate intake from fresh and preserved vegetables

Highest vs lowest



375 327 2 0.5 Low-est

0.3-08

Signif-icant

N/A Age, sex, total calories, ethnicity/ race, Subjects w/ mothers questionnaire

NAS00531

Ward

2000

Childhood Intake for Age 10: Nitrite from soybean products

Highest vs lowest quartile



375 327 4 0.6 Low-est

0.3-1.4

Not signif-icant

N/A Age, sex, ethnicity/ race, vegetable intake

NAS00531

Ward

2000

Childhood Intake for Age 3: Nitrite from soybean products




375 327 4 1.2 Low-est

0.4-3.0

Not signif-icant


NAS00531

Ward

2000

Intake During Weaning: Nitrite from soybean products




375 327 4 0.7 Low-est

0.3-1.4

Not signif-icant


NAS00531

Ward

2000

Mother's intake of nitrite during breast-feeding: from soybean products

Highest vs lowest tertile



375 327 3 0.7 Low-est

0.3-1.7

Not signif-icant

N/A N/A

1 June, 2006


215


Author, Yr


Assess-ment

Source

Country Ethnicity

of subjects

No of Populations analysed


No.

cases

No.

controls

No.

categories

Mean Ref group

CI P value Adjusted for

NAS06019

Huang

1982

Nitrites .007 - .029 g/L

pickles China Chinese 86 N/A/ Mixed

Wuhua: 61, Sihui: 86, Zhong-shang: 61

N/A 3 Sihui = .007

Zhong-shang = .029

Wuhua = .019g/L

N/A Sihui = <0.01

Zhong-shang = <0.05

Unadjusted

NAS06019

Huang

1982

Nitrates 9.76 – 13.78 g/L



N/A 3 Sihui = 9.76

Zhong-shang = 12.02

Wuhua = 13.78 g/L

N/A Sihui = >0.05

Zhong-shang = >0.05

Unadjusted

NAS06019

Huang

1982

Secondary amines

9.67 – 15.82 g/L



N/A 3 Sihui = 15.82

Zhong-shang = 14.36

Wuhua = 9.67 g/L

N/A Sihui = >0.05

Zhong-shang = >0.05

Unadjusted

NAS06041

Huang

1983

Nitrites 0-0.53 mg/L

rice China Chinese N/A N/A/ Mixed


N/A 3 Sihui = 0.13

Zhong-shang = 0.23

Wuhua = 0.23 mg/L

N/A Sihui = <0.01

Zhong-shang = >0.05

Unadjusted

NAS06041

Huang

1983

Nitrites 0-0.40 mg/L

drinking water



N/A 3 Sihui = .0018

Zhong-shang = .017

Wuhua = 0.01 mg/L

N/A Sihui = >0.05

Zhong-shang = <0.01

Unadjusted

NAS06041

Huang

1983

nitrates 0.13-17.44 mg/L

rice China Chinese N/A N/A/ Mixed


N/A 3 Sihui = 6.44

Zhong-shang = 1.14

Wuhua = 1.05 mg/L

N/A Sihui = <0.01

Zhong-shang = >0.05

Unadjusted

1 June, 2006


216

Study identifier

Author, Yr


Assess-ment

Source

Country Ethnicity

of subjects

No of Populations analysed


No.

cases

No.

controls

No.

categories

Mean Ref group

CI P value Adjusted for

NAS06041

Huang

1983

nitrates 0-43.28 mg/L

drinking water



N/A 3 Sihui = 2.26

Zhong-shang = 13.21

Wuhua = 2.33 mg/L

N/A Sihui = >0.05

Zhong-shang = <0.01

Unadjusted

NAS06041

Huang

1983

Secondary amines

0.34-99.46 mg/L

Pickled foods



N/A 3 Sihui = 15.52

Zhong-shang = 14.36

Wuhua = 9.67 mg/L

N/A Sihui = >0.05

Zhong-shang = >0.05

Unadjusted

NAS06043

Huang

1988

Nitrites and nitrates

3.9-13 ppb

pickles consumed by local residents

China, Taiwan

Chinese Case present the high risk area of NPC-Sihui county, Control present the low risk area of NPC-Wuhua County

N/A/ Mixed

45 36 2 Sihui = 13 ppb

Wuhua = 3.9 ppb

N/A <0.01 Unadjusted

4.4.1 Fresh food Fresh animal foods Fresh meat: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00577

Yuan

2000

Organ meat, fresh




N/A Unadusted

1 June, 2006


217

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

Fresh pork/beef liver, at age 10 and age 5 years prior to diagnosis






NAS00749

Armstrong

1998






1.89-11.3

N/A .009 Unadjusted

NAS01459

Yu

1989

Fresh meat, 3 years prior to diagnosis





NAS01922

Ning

1990






Fresh meat: Childhood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

fresh pork/beef liver, at age 10 and age 5 years prior to diagnosis






NAS00749

Armstrong

1998






0.51-2.46

N/A N/A Unadjusted

1 June, 2006


218

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01459

Yu

1989

Fresh meat, at age 10





NAS01459

Yu

1989

Fresh meat, at age 1-2





NAS01520

Yu

1988

fresh meats, during weaning




NAS01520

Yu

1988

fresh meats, ages 1-2




NAS01520

Yu

1988

fresh meats, at age 10




N/A Age, sex

NAS01922

Ning

1990






Fresh fish Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

1 June, 2006


219

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01459

Yu

1989

Fresh fish sauce, adult





NAS01459

Yu

1989

Fresh fish sauce, age 10





NAS01459

Yu

1989

Fresh fish sauce, age 1-2





NAS01520

Yu

1988

Fresh fish, age 10




N/A Age, sex

NAS01520

Yu

1988

Fresh fish, age 1-2




NAS01520

Yu

1988

Fresh fish, during weaning



128 174 N/A N/A N/A N/A 0.09 N/A Sex

NAS01922

Ning

1990






NAS01922

Ning

1990






Fresh seafood

1 June, 2006


220


Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00577

Yuan

2000

Seafood, fresh N/A FFQ - Study-specific



N/A N/A

NAS01922

Ning

1990

crab, fresh, at age 10




N/A N/A

NAS01922

Ning

1990

crab, fresh, 3 years prior to diagnosis




N/A N/A

NAS01922

Ning

1990

jellyfish, fresh, at age 10




N/A N/A

NAS01922

Ning

1990

jellyfish, fresh, 3 years prior to diagnosis




N/A N/A

NAS04944

Armstrong

1978

fresh prawns, at evening meal among families of cases / controls



N/A N/A

NAS04944

Armstrong

1978

fresh prawn in 3 main daily meals combined, among cases / controls


60 150 N/A 0.7 N/A N/A <0.05 N/A Age, sex, SES, ethnicity/ race, area of residence, lifestyle factors

Fresh eggs Case-control (3)

1 June, 2006


221

Study identifier

Author, Yr


Assess-ment Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS00577

Yuan

2000

Eggs, fresh N/A FFQ - Study-specific



N/A N/A

NAS01520

Yu

1988

fresh eggs during weaning




NAS01520

Yu

1988

fresh eggs, ages 1 to 2 years




NAS01520

Yu

1988

fresh eggs, at age 10




N/A Age, sex

NAS04944

Armstrong

1978

fresh eggs, at evening meal among families of cases and controls



N/A N/A

NAS04944

Armstrong

1978

fresh egg in three main daily meals, among cases/ controls




NAS04944

Armstrong

1978

Fresh egg, for breakfast among families of partici-pants



N/A N/A

Fresh milk Case-control (1)

1 June, 2006


222

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00577

Yuan

2000

Fresh milk




N/A Unadjusted

Fresh plant foods Fresh vegetables: Adulthood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

All fresh vegetables

≤ 538 times per year to > 866 times per year



935 1032 4 0.85 ≤ 538 times per year

0.65-1.10

N/A 0.13 Sex, Age, Education, Smoking, Exposure to smoke from heated rapeseed oil and burning coal while cooking, occupational exposure to chemical fumes, History of chronic ear and nose condition

NAS01922

Ning

1990

Fresh vegetable, consumption 3 years prior to diagnosis






Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Regression slope

Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


223

NAS00817

Koo

1997

Fresh vegetables


China, Hong Kong

Chinese N/A Male N/A N/A Continuous r2 = -0.77 N/A N/A 0.009 N/A age

NAS00817

Koo

1997

Fresh vegetables


China, Hong Kong

Chinese N/A Female N/A N/A Continuous r2 = -0.75 N/A N/A 0.013 N/A age

Fresh vegetables: Childhood/Infancy consumption Case-control (2) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Mother's diet during breastfeeding: Fresh vegetables

Highest vs lowest



375 327 N/A 0.3 Lowest 0.1-1/5

N/A N/A N/A

NAS01922

Ning

1990

Fresh vegetable, consumption at 10 years of age





Fresh green vegetables: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

Fresh green vegetables, consumption during weaning



306 306 2 0.6 No 0.3-1.1


1 June, 2006


224

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01459

Yu

1989

Fresh green vegetables, consumption during ages 1-2

Rarely to weekly



110 139 3 1.7 Weekly 0.6-4.9

N/A Not Signif icant

Age, Sex, Area of Residence

NAS01459

Yu

1989

Fresh green vegetables, consumption at age 10

Less than daily to daily



306 306 2 1.3 Daily 0.3-5.1


Other fresh vegetables Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS04944

Armstrong

1978

Fresh vegetables, at evening meal among families of participants


60 150 N/A OR < 1


N/A Unadjusted

Fresh cabbage: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Coun-try

Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Fresh Bok Choi (chinese white cabbage)




935 1032 3 0.97 Weekly 0.81-1.17


Fresh Green Leafy Vegetables: Adulthood consumption Case-control (1)

1 June, 2006


225

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Other dark green leafy vegetable (not bok choi) fresh





0.73-2.14


Fresh Green Leafy Vegetables: Childhood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01520

Yu

1988

fresh green leafy vegetables, during weaning




0.86 Age, sex

NAS01520

Yu

1988

fresh green leafy vegetables, between ages 1 to 2 years




0.92 Age, sex

NAS01520

Yu

1988

fresh leafy green vegetables, at age 10




N/A Age, sex

Fresh Tomatoes: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


226

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Tomatoes, fresh





N/A N/A 0.10 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition, oranges/ tangerines

Other Fresh Vegetables: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Light green/ orange leafy vegetables, fresh





0.63-1.5


NAS00577

Yuan

2000

Gourds, fresh Less than weekly to daily




0.73-1.09


NAS00577

Yuan

2000

Green peppers, fresh





N/A N/A 0.43 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition, oranges/tangerines

Fresh fruits: Adulthood consumption Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

1 June, 2006


227

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories


p value for trend

Adjusted for

NAS01141

Zheng

1994

Fresh fruit, in the past 7 years




N/A N/A

NAS01922

Ning

1990

fresh fruit, 3 years prior to diagnosis





NAS04944

Armstrong

1978

Fresh fruit, at evening meal, families of participants



N/A Unadjusted

NAS06030

Huang

2002

Fresh fruits Less to frequently consumed

Question-naire



0.44-1.04


Fresh fruits: Childhood consumption Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01141

Zheng

1994

Fresh fruit, ages 0-3




N/A N/A

NAS01141

Zheng

1994

Fresh fruit, age of 10




N/A N/A

1 June, 2006


228

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

Fresh fruit, at age 10





NAS60010

Cai

1996

fresh fruit, consumed around 1968 and <3 times/ week




115 115 2 1.502 ≥ 12 times per month

1.11-2.03


NAS60010

Cai

1996

fresh fruit, consumed around 1978, < 3 time/week




115 115 2 1.471 ≥ 12 times per month

1.12-1.94


Fresh citrus fruit: Adulthood consumption Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Oranges and tangerines, fresh





N/A N/A 0.0005 Age, sex, area of residence, environmental factors, smoking, chemical fumes, history of ear/nose condition, green/red peppers, tomatoes, & green beans/peas

Other fresh fruits: Childhood consumption Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

1 June, 2006


229

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01459

Yu

1989

other fresh fruits (not oranges/ tangerines), ages 1-2

Rarely to weekly



110 139 3 0.6 Rarely 0.3-1.2



NAS01459

Yu

1989

other fresh fruits (not oranges/ tangerines), at age 10

Rarely to daily



110 139 4 0.3 Rarely 0.1-1.1



NAS01520

Yu

1988

other fresh fruits (not oranges / tangerines) ages 1 to 2




N/A Age, sex

NAS01520

Yu

1988

other fresh fruits (not oranges/ tangerines at age 10




N/A Age, sex

Fresh pulses/legumes Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000

Adult Dietary Intake: consumption of fresh soybean products

Never vs. ever


China, Taiwan




NAS00531

Ward

2000


≤1.96

grams to ≥ 6.4 grams


China, Taiwan


93 114 4 0.4 ≤1.96 grams

0.2-1.0

N/A N/A Age, sex, ethnicity/ race, total calories, mothers questionnaire

1 June, 2006


230

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00531

Ward

2000


≤1,6 grams to > 4 grams


China, Taiwan


90 110 4 0.7 ≤1,6 grams

0.3-1.7


NAS00531

Ward

2000

During Weaning: Fresh soybean products

None to > 0 grams


China, Taiwan


84 104 2 1.1 None 0.5-1.2


NAS00531

Ward

2000


Lowest to highest


China, Taiwan


375 327 3 0.7 Lowest 0.3-1.6

N/A N/A Age, sex, ethnicity/ race, Vegetable intake

NAS00531

Ward

2000


Lowest to highest


China, Taiwan


375 327 3 0.6 Lowest 0.2-1.5

N/A N/A N/A

Mixed vegetables Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00577

Yuan

2000

Fresh green beans and peas





0.62-0.99


4.4.1.1 Raw Case-control (2)

1 June, 2006


231

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS00749

Armstrong

1998

Raw green vegetables




282 282 3 0.5 Monthly 0.23-1.07

N/A .026 Unadjusted

NAS04944

Armstrong

1978

Sliced raw chili

At evening meals


60 150 2 N/A N/A N/A Cases ate less at evening meals

N/A Unadjusted

4.4.2 Cooked food Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01113

Zheng

1994






NAS01113

Zheng

1994






NAS01922

Ning

1990


Ever vs Never



100 300 2 1.6 Never 0.8-3.2


4.4.2.1 Steaming, boiling, poaching Case-control (1)

1 June, 2006


232

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990






NAS01922

Ning

1990






NAS01922

Ning

1990


Ever vs Never



100 300 2 4.2 Never 2.2-8.3


4.4.2.2 Stewing, casseroling Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01381

Jeannel

1990

Dietary Intake During Weaning: Stewing mixture (red pepper, black pepper, caraway, coriander, oil, salt and garlic)



80 160 2 8.4 No N/A <0.005 N/A Sex, age, lifestyle factors, area of residence

NAS01381

Jeannel

1990

Dietary Intake During Preceding Year to Diagnosis: Stewing mixture (red pepper, black pepper, caraway, coriander, oil, salt and garlic)



80 160 2 4.4 No N/A 0.04 N/A Sex, age, lifestyle factors, area of residence

4.4.2.5 Frying

1 June, 2006


233


Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

OR Ref group


Adjusted for

NAS01922

Ning

1990

Fried food, 3 years prior to diagnosis





NAS01922

Ning

1990

Fried food, at 10 years of age





4.4.2.6 Grilling (broiling) and barbecuing Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS01922

Ning

1990

grilled food, 3 years prior to diagnosis





NAS01922

Ning

1990

grilled food, at 10 years of age





5.3.1 Total protein Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories


p value for trend

Adjusted for

1 June, 2006


234

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories


p value for trend

Adjusted for

NAS00577

Yuan

2000

All protein-containing preserved foods

Quantiles: 0 to 97+ times per year



935 1032 4 1.78 Lowest quantile: 13 times per year

1.37-2.31

Signif-icant

0.001 Sex, Age, Educational Level, Smoking, Exposure to smoke from heated rapeseed oil and burning coal while cooking, Occupational exposure to chemical fumes, History of chronic ear and nose condition

5.5.1 Vitamin A Case-control (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group


Adjusted for

NAS02182

Armstrong

1983

Foods rich in vitamin A

N/A Hospital records

Malaysia Chinese N/A Mixed 87 79 2 N/A N/A N/A Not signif-icant

N/A Sex, area of residence, ethnicity/ race, age

5.5.1.2.1 Beta-carotene Beta-carotene Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00700

Farrow

1998

beta carotene

Lowest to highest

FFQ – Block

United States


129 206 4 0.47 Lowest 0.22-1.02


1 June, 2006


235

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS01056

Lee

1994

beta-carotene, during adulthood

Highest v. lowest tertile



64 102 3 0.7 lowest 0.4-1.2


5.5.9 Vitamin C Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Con-trols

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00700

Farrow

1998

Vitamin C Lowest to highest

FFQ – Block

United States


129 206 4 0.50 Lowest 0.24-1.04


NAS01056

Lee

1994

Vitamin C, during adulthood




N/A Age, sex, education, ethnicity/ race, other nutrients

NAS02182

Armstrong

1983

Foods rich in vitamin C

N/A Hospital records

Malaysia Chinese N/A Mixed 87 79 2 N/A N/A N/A Not signif-icant

N/A Sex, area of residence, ethnicity/ race, age

5.5.10 Vitamin D (and calcium) Case-control (1) Study identifier

Author, Yr


Assess-ment

Source

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

1 June, 2006


236

NAS02696

Man

1996

Calcium (and Vitamin D), detected in hair sample


Hair Sample


23 69 2 cases: 1022

controls: 1302


N/A Unadjusted

Cross-sectional (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Mean for cases

Mean for controls

t P value

Adjusted for

NAS06005

Li

1996

Calcium (and Vitamin D)

2.0678-2.3006

Serum China Chinese 380 20-60/ Mixed

66 314 2 Cases = 2.0678

Controls = 2.3006

3.3381 <0.05 Unadjusted


Author, Yr


Assessment

Source

Country Ethnicity

of subjects

No of populations analysed

Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

Mean for cases

Mean for controls

t P value

Adjusted for

NAS06005

Li

1996


24.545-76.28

Ca concentration in drinking water

China Chinese Case represent Sihui, Control represent Meizhou

N/A 190 53 2 Cases = 24.545

Controls = 76.28

8.377 <.001 Unadjusted

NAS06005

Li

1996


2.238-2.358

Ca concentration in serum


N/A 190 53 2 Cases = 2.238

Controls = 2.358


5.5.11 Vitamin E Case-control (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

1 June, 2006


237

NAS01056

Lee

1994

Vitamin E, during adulthood

Lowest v. highest



64 102 3 0.5 Lowest 0.3-0.8

Signif-icant

.001 Age, sex, education, ethnicity/ race

5.5.13 Other vitamins (including multivitamins) Multi-Vitamins, supplements only Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

OR Ref group

CI P value

p value for trend

Adjusted for

NAS00700

Farrow

1998

Other vitamins, Multivitamin use

Yes or no FFQ – Block

United States


129 206 2 0.56 No 0.31-1.01

N/A N/A Age, Sex, Energy Intake, Alcohol consumption, Smoking Habits

NAS00700

Farrow

1998

Other vitamins, supplements

Yes or no FFQ – Block

United States


129 206 2 0.55 No 0.31-1.01

N/A N/A Age, Sex, Energy Intake, Alcohol consumption, Smoking Habits

5.6.2 Iron Case-control (3) Study identifier

Author, Yr


Assessment

Source

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Controls

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS06012

Deng

1995

serum Fe concentration




44 42 2 Mean cases: 388.19


Cases: 267-509

Controls: 315-466

>0.05 N/A Unadjusted

1 June, 2006


238

Study identifier

Author, Yr


Assessment

Source

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Controls

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS06012

Deng

1995

Fe concentration in drinking water


in drinking water


44 42 2 Mean cases: 14.70



NAS06012

Deng

1995

Fe concentration in rice


in rice China Chinese 86 20-60/ Mixed

44 42 2 Mean cases: 13.53



NAS01865

Robinson

1968

Iron on maize leaf


maize leaf Kenya Central Bantu and Nilo-Hamitic

100 N/A/ N/A 50 50 2 Mean cases: 695

Mean controls: 644



NAS02696

Man

1996

Iron, detected in hair sample



12 38 2 cases: 58.8

controls: 35.8


5.6.3 Calcium (and vitamin D) Case-control (1) Study identifier

Author, Yr


Assess-ment

Source

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS02696

Man

1996

Calcium (and Vitamin D), detected in hair sample


Hair Sample


23 69 2 cases: 1022

controls: 1302


N/A Unadjusted

Cross-sectional (1) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Mean for cases

Mean for controls

t P value

Adjusted for

1 June, 2006


239

NAS06005

Li

1996


2.0678-2.3006

Serum China Chinese 380 20-60/ Mixed

66 314 2 Cases = 2.0678

Controls = 2.3006

3.3381 <0.05 Unadjusted


Author, Yr


Assessment

Source

Country Ethnicity

of subjects

No of populations analysed

Age/Sex of subjects

No.

cases

No.

controls

No.

Cate-gories

Mean for cases

Mean for controls

t P value

Adjusted for

NAS06005

Li

1996


24.545-76.28

Ca concentration in drinking water


N/A 190 53 2 Cases = 24.545

Controls = 76.28


NAS06005

Li

1996


2.238-2.358

Ca concentration in serum


N/A 190 53 2 Cases = 2.238

Controls = 2.358


5.6.4 Selenium Case-control (3) Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS01145

Lajtman

1994

Selenium Mean exposure cases vs. controls

Serum, atomic absorption methods

Zagreb Croatia

Croatian 81 37-78/ Mixed

34 47 2 Mean cases: 59.27



NAS01402

Yang

1990

Selenium Mean exposure cases vs. controls

Serum, fluorometric method


111 56 2 Mean cases: 0.109



1 June, 2006


240

Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS06012

Deng

1995

serum Se concentration




44 42 2 Mean cases: 49.17


Cases: 40.8-57.6

Controls: 73.4-95.7


NAS06012

Deng

1995

Se concentration in drinking water


in drinking water


44 42 2 Mean cases: 0.06

Mean controls: 0.11


NAS06012

Deng

1995

Se concentration in rice



44 42 2 Mean cases: 20.13



5.6.5 Iodine Case-control (1) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects


Age/Sex of subjects

No.

cases

No.

controls

No.

categories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS02696

Man

1996

Iodine, detected in hair sample


Hair Sample


8 30 2 cases: 1.038

controls: 0.56


N/A Unadjusted

5.6.6 Other minerals Chromium Case-control (2)

1 June, 2006


241

Study identifier

Author, Yr


Assessment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS02012

Ling-Wei

1988

Chromium, in drinking water


Unknown-NA China Chinese 75 N/A/ N/A

45 30 2 Median cases: 4.0



NAS06012

Deng

1995

serum Chromium (Cr) concentration




44 42 2 Mean cases: 65.56


Cases: 53.3-77.8

Controls: 33.0-45.2


NAS06012

Deng

1995

Chromium (Cr) concentration in drinking water


in drinking water


44 42 2 Mean cases: 0.42

Mean controls: 0.28


NAS06012

Deng

1995

Chromium (Cr) concentration in rice



44 42 2 Mean cases: 140.75



Copper Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS01865

Robinson

1968

Copper, in maize leaf


Unknown-NA

Kenya Central Bantu and Nilo-Hamitic

100 N/A/ N/A

49 49 2 Mean cases: 15.5

Mean controls: 15.8



NAS02012

Ling-Wei

1988

Copper, in drinking water


Unknown-NA

China Chinese 75 N/A/ N/A

45 30 2 Median cases: 2.6



1 June, 2006


242

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS02696

Man

1996

copper, detected in hair sample



24 78 2 cases: 14.25

controls: 14.29


N/A Unadjusted

NAS06012

Deng

1995

serum Copper concentration




44 42 2 Mean cases: 0.50

Mean controls: 0.52

Cases: 0.25-0.75

Controls: 0.35-0.69

>0.05 N/A Unadjusted

NAS06012

Deng

1995

Copper concentration in drinking water


in drinking water


44 42 2 Mean cases: 1.82

Mean controls: 1.33


NAS06012

Deng

1995

Copper concentration in rice



44 42 2 Mean cases: 30.32



Manganese Case-control (3) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS01865

Robinson

1968

Manganese, in maize leaf


Unknown-NA


100 N/A/ N/A 49 49 2 Mean cases: 128

Mean controls: 123



NAS02012

Ling-Wei

1988

Manganese, in drinking water


Unknown-NA

China Chinese 75 N/A/ N/A 45 30 2 Median cases: 7.6



1 June, 2006


243

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS02696

Man

1996

Manganese, detected in hair sample


Hair Sample


26 75 2 cases: 2.12

controls: 2.41


N/A Unadjusted

Zinc Case-control (4) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS01865

Robinson

1968

Zinc, in maize leaf


Unknown-NA


100 N/A/ N/A 50 50 2 Mean cases: 30.2

Mean controls: 30.2



NAS02012

Ling-Wei

1988

Zinc, in drinking water


Unknown-NA

China Chinese 75 N/A/ N/A 45 30 2 Median cases: 12.0



NAS02696

Man

1996

zinc, detected in hair sample



25 74 2 cases: 199.92

controls: 210.16


N/A Unadjusted

NAS06012

Deng

1995

serum zinc concentration




44 42 2 Mean cases: 4.24

Mean controls: 4.72

Cases: 3.11-5.37

Controls: 3.72-5.72


NAS06012

Deng

1995

zinc concentration in drinking water


in drinking water


44 42 2 Mean cases: 3.65

Mean controls: 4.71


1 June, 2006


244

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS06012

Deng

1995

zinc concentration in rice



44 42 2 Mean cases: 8.41



Other minerals Case-control (2) Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS01865

Robinson

1968

Boron, in maize leaf


Unknown-NA


100 N/A/ N/A 41 41 2 cases: 14.8

controls: 14.9



NAS02696

Man

1996

aluminum, detected in hair sample


Hair Sample


26 76 2 cases: 15.62

controls: 15.26


N/A Unadjusted

NAS02696

Man

1996

antimony, detected in hair sample


Hair Sample


25 61 2 cases: 0.221

controls: 0.173


N/A Unadjusted

NAS02696

Man

1996

magnesium, detected in hair sample


Hair Sample


29 72 2 cases: 134.1

controls: 137.5


N/A Unadjusted

NAS02696

Man

1996

potassium, detected in hair sample


Hair Sample


24 64 2 cases: 22.46

controls: 18.72


N/A Unadjusted

1 June, 2006


245

Study identifier

Author, Yr


Assess-ment

Tool

Country Ethnicity

of subjects



No.

cases

No.

Con-trols

No.

Cate-gories

Mean for cases

Mean for controls

CI P value

p value for trend

Adjusted for

NAS02696

Man

1996

strontium, detected in hair sample


Hair Sample


19 59 2 cases: 4.332

controls: 6.532


NAS02696

Man

1996

sulfur, detected in hair sample


Hair Sample


29 95 2 cases: 6.21

controls: 5.89


N/A Unadjusted

NAS02696

Man

1996

vanadium, detected in hair sample


Hair Sample


20 85 2 cases: 263.1

controls: 85.5


Documents

Nasopharynx SLR