Risk factors for lung cancer A systematic review
2014
Risk factors for lung cancer: a
systematic review
Final Report
2014
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Risk factors for lung cancer: A systematic review i
Foreword
Lung cancer is the fourth most common cancer diagnosed in both men and women in
Australia and the leading cause of cancer death.
Risk factors for lung cancer: a systematic review is a comprehensive systematic review of the
international literature commissioned by Cancer Australia.
This systematic review provides a detailed analysis of the key lifestyle, environmental and
occupational factors that affect lung cancer risk, in addition to the role of family history. The
systematic review also highlights factors where the evidence is either limited or inconsistent in
relation to risk of lung cancer.
We anticipate the systematic review and the Risk factors for lung cancer: an overview, a
summary of the systematic review, will be a valuable resource to support health
professionals, policy makers and the community with evidence about exposure to risk factors
for lung cancer, to increase understanding of those who may be at greatest risk of lung
cancer and to inform interventions to ultimately reduce the burden of lung cancer.
Helen Zorbas AO
CEO
Cancer Australia
Risk factors for lung cancer: A systematic review ii
Contents
Foreword……… .....................................................................................................................................i
Acknowledgments ....................................................................................................................... xxviii
1 Introduction............................................................................................................................. 1
2 Methods .................................................................................................................................. 3
2.1 Inclusion criteria .............................................................................................................. 3
2.1.1 Types of participants ...................................................................................... 3
2.1.2 Types of intervention/Exposures of interest ............................................... 3
2.1.3 Types of outcome .......................................................................................... 4
2.1.4 Types of studies ............................................................................................... 4
2.2 Search strategy and study selection .......................................................................... 6
2.3 Critical appraisal ............................................................................................................ 7
2.4 Data extraction and synthesis ..................................................................................... 7
2.5 Use of the IARC monographs ....................................................................................... 8
3 Results ………………………………………………………………………………………………….9
3.1 Introduction ..................................................................................................................... 9
3.2 Results of database search, study selection and inclusion ................................. 15
4 Risk factor: Active smoking and passive smoking .......................................................... 17
4.1 Introduction ................................................................................................................... 17
4.2 Results ............................................................................................................................. 26
4.2.1 Active smoking and risk of lung cancer .................................................. 26
4.2.2 Active smoking, gender and risk of lung cancer ................................... 26
4.2.3 Passive smoking and risk of lung cancer ................................................. 27
4.2.4 Other forms of tobacco smoking .............................................................. 28
4.3 Summary ........................................................................................................................ 28
4.4 Conclusions.................................................................................................................... 29
4.4.1 Hazard identification ................................................................................... 29
4.4.2 Risk assessment ............................................................................................. 30
4.5 Methodological quality of studies ............................................................................ 31
5 Risk factor: Asbestos exposure ........................................................................................... 34
5.1 Introduction ................................................................................................................... 34
5.2 Results ............................................................................................................................. 41
5.2.1 Occupational exposure to asbestos and risk of lung cancer ............. 41
5.2.2 Non-occupational exposure to asbestos and risk of lung
cancer ............................................................................................................ 48
5.2.3 Asbestos exposure, gender and risk of lung cancer ............................. 49
5.2.4 Asbestos exposure, smoking status and risk of lung cancer ................ 50
5.2.5 Asbestosis, asbestos exposure and risk of lung cancer ........................ 52
5.2.6 Type of asbestos and risk of lung cancer ................................................ 53
5.3 Summary ........................................................................................................................ 54
5.4 Conclusion ..................................................................................................................... 55
5.4.1 Hazard identification ................................................................................... 55
5.4.2 Risk assessment ............................................................................................. 55
5.5 Methodological quality of studies ............................................................................ 56
6 Risk factor: Radon exposure ............................................................................................... 59
6.1 Introduction ................................................................................................................... 59
6.1.1 Occupational exposure to radon in Australia ........................................ 59
6.1.2 Residential exposure to radon in Australia .............................................. 60
6.2 Results ............................................................................................................................. 73
6.2.1 Occupational radon exposure and risk of lung cancer....................... 73
6.2.2 Occupational radon exposure and risk of lung cancer: Joint
effects with smoking .................................................................................... 74
6.2.3 Residential radon exposure and risk of lung cancer ............................. 76
6.2.4 Residential radon exposure and risk of lung cancer in Europe .......... 76
6.2.5 Residential radon exposure and risk of lung cancer in the US ............ 77
6.2.6 Residential radon exposure and risk of lung cancer in China ............ 77
6.2.7 Level of residential radon exposure and risk of lung cancer .............. 78
Risk factors for lung cancer: A systematic review iv
6.2.8 Residential radon exposure, smoking status and risk of lung
cancer ............................................................................................................ 78
6.2.9 Residential radon exposure, gender and risk of lung cancer ............. 79
6.3 Summary ........................................................................................................................ 80
6.4 Conclusion ..................................................................................................................... 80
6.4.1 Hazard identification ................................................................................... 80
6.4.2 Risk assessment ............................................................................................. 80
6.5 Methodology quality of studies ................................................................................. 82
7 Risk factor: Arsenic exposure ............................................................................................. 87
7.1 Introduction ................................................................................................................... 87
7.2 Results ............................................................................................................................. 94
7.2.1 Inhalational arsenic exposure and risk of lung cancer ......................... 94
7.2.2 Smelter workers and living near smelters ................................................. 95
7.2.3 Miners .............................................................................................................. 99
7.2.4 Smelter workers and miners ...................................................................... 102
7.2.5 Fertiliser manufacturing plant, stoking, pesticide and refinery
workers .......................................................................................................... 102
7.2.6 Inhalational arsenic exposure and risk of lung cancer by
smoking status ............................................................................................. 104
7.2.7 Inhalational arsenic exposure and risk of lung cancer by
gender .......................................................................................................... 105
7.2.8 Ingested arsenic exposure (drinking water) and risk of lung
cancer .......................................................................................................... 106
7.2.9 Ingested arsenic exposure (drinking water) and risk of lung
cancer by smoking status ......................................................................... 108
7.2.10 Ingested arsenic exposure (drinking water) and risk of lung
cancer by gender ...................................................................................... 109
7.3 Summary ...................................................................................................................... 109
7.4 Conclusion ................................................................................................................... 110
7.4.1 Hazard identification ................................................................................. 110
7.4.2 Risk assessment ........................................................................................... 111
Methodological quality of studies ........................................................................................ 112
8 Risk factor: Polycyclic aromatic hydrocarbons (PAHs) ................................................ 115
8.1 Introduction ................................................................................................................. 115
8.2 Results ........................................................................................................................... 123
8.2.1 Occupational exposure to PAH and risk of lung cancer ................... 123
8.2.2 Occupational PAH exposure and risk of lung cancer in coal
gasification workers ................................................................................... 125
8.2.3 Occupational exposure to PAHs and risk of lung cancer in
coke production workers .......................................................................... 127
8.2.4 Occupational PAH exposure and risk of lung cancer in
creosote workers ........................................................................................ 128
8.2.5 Occupational PAH exposure and risk of lung cancer in
aluminium production workers ................................................................ 128
8.2.6 Occupational PAH exposure and risk of lung cancer in
chimney sweeps and in workers exposed to soot ............................... 130
8.2.7 Occupational PAH exposure, smoking status and risk of lung
cancer .......................................................................................................... 130
8.2.8 Occupational PAH exposure, gender and risk of lung cancer ........ 131
8.3 Summary ...................................................................................................................... 132
8.4 Conclusion ................................................................................................................... 132
8.4.1 Hazard identification ................................................................................. 132
8.4.2 Risk assessment ........................................................................................... 132
8.5 Methodological quality of studies .......................................................................... 133
9 Risk factor: Family history .................................................................................................. 136
9.1 Introduction ................................................................................................................. 136
9.2 Results ........................................................................................................................... 139
9.2.1 Family history and risk of lung cancer .................................................... 139
9.2.2 Family history, smoking status and risk of lung cancer ........................ 139
9.2.3 Family history, gender and risk of lung cancer ..................................... 140
9.2.4 Risk of lung cancer by family member affected ................................. 140
9.3 Summary ...................................................................................................................... 140
9.4 Conclusion ................................................................................................................... 141
9.4.1 Hazard identification ................................................................................. 141
Risk factors for lung cancer: A systematic review vi
9.4.2 Risk assessment ........................................................................................... 141
9.5 Methodological quality of studies .......................................................................... 142
10 Risk factor: Iron and steel founding ................................................................................. 144
10.1 Introduction ................................................................................................................. 144
10.2 Results ........................................................................................................................... 148
10.2.1 Overall risk of lung cancer in iron and steel foundry workers ............ 148
10.2.2 Risk of lung cancer for workers in iron and steel foundries, by
exposure to specific agents ..................................................................... 149
10.2.3 Risk of lung cancer in iron and steel foundry workers, by job
category ...................................................................................................... 150
10.2.4 Risk of lung cancer in iron and steel foundry workers, by
duration of employment ........................................................................... 151
10.2.5 Risk of lung cancer in iron and steel foundry workers by
smoking status ............................................................................................. 153
10.2.6 Risk of lung cancer in iron and steel foundry workers by gender ..... 154
10.3 Summary ...................................................................................................................... 154
10.4 Conclusion ................................................................................................................... 155
10.4.1 Hazard identification ................................................................................. 155
10.4.2 Risk assessment ........................................................................................... 155
10.5 Methodological quality of included studies ......................................................... 156
11 Risk factor: Silica exposure ............................................................................................... 158
11.1 Introduction ................................................................................................................. 158
11.2 Results ........................................................................................................................... 167
11.2.1 Occupational silica exposure and risk of lung cancer ....................... 167
11.2.2 Duration of silica exposure and risk of lung cancer ............................ 170
11.2.3 Intensity of silica exposure and risk of lung cancer ............................. 171
11.2.4 Silica exposure and risk of lung cancer in people with silicosis ......... 172
11.2.5 Silica exposure, smoking status and risk of lung cancer ..................... 174
11.3 Summary ...................................................................................................................... 174
11.4 Conclusion ................................................................................................................... 175
11.4.1 Hazard identification ................................................................................. 175
11.4.2 Risk assessment ........................................................................................... 175
11.5 Methodological quality of studies .......................................................................... 176
12 Risk factor: Nickel exposure ............................................................................................. 179
12.1 Introduction ................................................................................................................. 179
12.2 Results ........................................................................................................................... 187
12.2.1 Occupational nickel exposure and risk of lung cancer ..................... 187
12.2.2 Duration of nickel exposure and risk of lung cancer .......................... 188
12.2.3 Cumulative exposure to nickel ................................................................ 188
12.2.4 Occupational nickel exposure, smoking status and risk of lung
cancer .......................................................................................................... 189
12.2.5 Occupational nickel exposure, type of nickel compound and
risk of lung cancer ...................................................................................... 190
12.3 Summary ...................................................................................................................... 191
12.4 Conclusion ................................................................................................................... 191
12.4.1 Hazard identification ................................................................................. 191
12.4.2 Risk assessment ........................................................................................... 191
12.5 Methodological quality of studies .......................................................................... 192
13 Risk factor: Painting as an occupation ............................................................................ 194
13.1 Introduction ................................................................................................................. 194
13.2 Results ........................................................................................................................... 200
13.2.1 Overall lung cancer risk associated with any duration of work
as a painter/various levels of exposure ................................................. 200
13.2.2 Wood and gypsum paints and overall risk of lung cancer ................ 201
13.2.3 Dose response for painting as an occupation and lung cancer
risk .................................................................................................................. 202
13.2.4 Risk of lung cancer from occupational exposure to paint by
gender .......................................................................................................... 203
13.3 Summary ...................................................................................................................... 203
13.4 Conclusion ................................................................................................................... 204
13.4.1 Hazard identification ................................................................................. 204
13.4.2 Risk assessment ........................................................................................... 205
Risk factors for lung cancer: A systematic review viii
13.5 Methodological quality of studies .......................................................................... 206
14 Risk factor: Cadmium exposure ....................................................................................... 209
14.1 Introduction ................................................................................................................. 209
14.2 Results ........................................................................................................................... 215
14.2.1 Occupational exposure to cadmium and risk of lung cancer ......... 215
14.2.2 Duration and intensity of occupational cadmium exposure
and risk of lung cancer ............................................................................. 217
14.2.3 Residential exposure to cadmium and risk of lung cancer ............... 221
14.2.4 Cadmium exposure, smoking status and risk of lung cancer............ 222
14.3 Summary ...................................................................................................................... 222
14.4 Conclusion ................................................................................................................... 223
14.4.1 Hazard identification ................................................................................. 223
14.4.2 Risk assessment ........................................................................................... 224
14.5 Methodological quality of studies .......................................................................... 225
15 Risk factor: Air pollution ..................................................................................................... 228
15.1 Introduction ................................................................................................................. 228
15.2 Results ........................................................................................................................... 235
15.2.1 Risk of lung cancer associated with exposure to fine
particulate matter (PM2.5) ......................................................................... 235
15.2.2 Risk of lung cancer associated with exposure to fine
particulate matter (PM2.5) and gender .................................................. 235
15.2.3 Risk of lung cancer associated with exposure to sulphur
dioxide (SO2) ............................................................................................... 236
15.2.4 Risk of lung cancer associated with exposure to sulphur
dioxide (SO2) and gender ........................................................................ 236
15.2.5 Risk of lung cancer associated with exposure to nitrogen
dioxide (NO2)............................................................................................... 237
15.2.6 Risk of lung cancer associated with exposure to nitrogen
oxides (NOx) ................................................................................................. 237
15.2.7 Risk of lung cancer associated with exposure to nitrogen
oxides (NOx) and smoking status. ........................................................... 237
15.2.8 Risk of lung cancer associated with exposure to vehicular
traffic ............................................................................................................. 238
15.2.9 Risk of lung cancer associated with exposure to vehicular
traffic and smoking status ......................................................................... 239
15.3 Summary ...................................................................................................................... 239
15.4 Conclusion ................................................................................................................... 240
15.4.1 Hazard identification ................................................................................. 240
15.4.2 Risk assessment ........................................................................................... 240
15.5 Methodological quality of studies .......................................................................... 242
16 Risk factor: Chromium exposure ...................................................................................... 244
16.1 Introduction ................................................................................................................. 244
16.2 Results ........................................................................................................................... 251
16.2.1 Occupational exposure to chromium and risk of lung cancer ........ 251
16.2.2 Duration of chromium exposure and risk of lung cancer................... 253
16.2.3 Chromium exposure, smoking status and risk of lung cancer ........... 254
16.3 Summary ...................................................................................................................... 254
16.4 Conclusion ................................................................................................................... 255
16.4.1 Hazard identification ................................................................................. 255
16.4.2 Risk assessment ........................................................................................... 255
16.5 Methodological quality of studies .......................................................................... 256
17 Risk factor: Beryllium exposure ........................................................................................ 258
17.1 Introduction ................................................................................................................. 258
17.2 Results ........................................................................................................................... 267
17.2.1 Occupational beryllium exposure and overall risk of lung
cancer .......................................................................................................... 267
17.2.2 Dose response for occupational beryllium exposure and risk of
lung cancer ................................................................................................. 270
17.2.3 Beryllium exposure, gender, smoking status and risk of lung
cancer .......................................................................................................... 271
17.3 Summary ...................................................................................................................... 271
17.4 Conclusion ................................................................................................................... 272
17.4.1 Hazard identification ................................................................................. 272
17.4.2 Risk assessment ........................................................................................... 272
Risk factors for lung cancer: A systematic review x
17.5 Methodological quality of studies .......................................................................... 273
18 Risk factor: Red meat and processed meat consumption ........................................... 276
18.1 Introduction ................................................................................................................. 276
18.2 Results ........................................................................................................................... 284
18.2.1 Red meat consumption and overall risk of lung cancer .................... 284
18.2.2 Red meat consumption, smoking status and risk of lung cancer .... 285
18.2.3 Red meat consumption and risk of lung cancer by gender ............. 287
18.2.4 Processed meat consumption and risk of lung cancer ...................... 288
18.2.5 Processed meat consumption, smoking status and risk of lung
cancer .......................................................................................................... 289
18.2.6 Processed meat consumption and risk of lung cancer by
gender .......................................................................................................... 290
18.3 Summary ...................................................................................................................... 290
18.4 Conclusion ................................................................................................................... 291
18.4.1 Hazard identification ................................................................................. 291
18.4.2 Risk assessment ........................................................................................... 291
18.5 Methodology quality of studies ............................................................................... 292
19 Risk factor: Alcohol consumption .................................................................................... 296
19.1 Introduction ................................................................................................................. 296
19.2 Results ........................................................................................................................... 306
19.2.1 Alcohol consumption and risk of lung cancer in the general
population ................................................................................................... 306
19.2.2 Alcohol consumption, smoking status and risk of lung cancer ......... 307
19.2.3 Alcohol consumption, gender and lung cancer risk .......................... 308
19.2.4 Types of alcoholic beverage consumed and risk of lung
cancer .......................................................................................................... 309
19.2.5 Alcohol consumption and risk of lung cancer in alcoholics .............. 310
19.3 Summary ...................................................................................................................... 311
19.4 Conclusion ................................................................................................................... 311
19.4.1 Hazard identification ................................................................................. 311
19.4.2 Risk assessment ........................................................................................... 312
19.5 Methodological quality of studies .......................................................................... 313
20 Risk factor: Dietary cholesterol and blood cholesterol ................................................. 318
20.1 Introduction ................................................................................................................. 318
20.2 Results ........................................................................................................................... 328
20.2.1 Dietary cholesterol intake and overall risk of lung cancer ................ 328
20.2.2 Risk of lung cancer and dietary cholesterol intake by smoking
status ............................................................................................................. 328
20.2.3 Dietary cholesterol intake, gender and risk of lung cancer .............. 329
20.3 Risk of lung cancer and blood cholesterol concentration ................................ 332
20.4 Risk of lung cancer and blood cholesterol by gender ....................................... 332
20.5 Summary ...................................................................................................................... 334
20.5.1 Dietary cholesterol and risk of lung cancer .......................................... 334
20.5.2 Blood cholesterol concentration and risk of lung cancer ................. 334
20.6 Conclusion ................................................................................................................... 334
20.6.1 Hazard identification ................................................................................. 334
20.6.2 Risk assessment ........................................................................................... 334
20.7 Methodological quality of studies .......................................................................... 336
21 Risk factor: Avian exposure .............................................................................................. 342
21.1 Introduction ................................................................................................................. 342
21.2 Results ........................................................................................................................... 345
21.2.1 Avian exposure and risk of lung cancer ................................................ 345
21.2.2 Duration of avian exposure and risk of lung cancer ........................... 346
21.2.3 Avian exposure, smoking status and risk of lung cancer ................... 346
21.2.4 Avian exposure, gender and risk of lung cancer ................................ 346
21.3 Summary ...................................................................................................................... 347
21.4 Conclusion ................................................................................................................... 347
21.4.1 Hazard identification ................................................................................. 347
21.4.2 Risk assessment ........................................................................................... 348
21.5 Methodological quality of studies .......................................................................... 349
22 Risk factor: Wood dust ....................................................................................................... 351
Risk factors for lung cancer: A systematic review xii
22.1 Introduction ................................................................................................................. 351
22.2 Results ........................................................................................................................... 360
22.2.1 Wood dust exposure and risk of lung cancer ....................................... 360
22.2.2 Wood dust exposure and risk of lung cancer by gender .................. 360
22.2.3 Wood dust exposure and risk of lung cancer by smoking status ..... 361
22.2.4 Dose response relationship between wood dust exposure and
lung cancer ................................................................................................. 361
22.3 Summary ...................................................................................................................... 362
22.4 Conclusion ................................................................................................................... 362
22.4.1 Hazard Identification ................................................................................. 362
22.4.2 Risk assessment ........................................................................................... 363
22.5 Methodological quality of included studies ......................................................... 364
23 Risk factor: Physical activity.............................................................................................. 367
23.1 Introduction ................................................................................................................. 367
23.2 Results ........................................................................................................................... 372
23.2.1 Physical activity and risk of lung cancer ............................................... 372
23.2.2 Physical activity, gender and risk of lung cancer ................................ 373
23.2.3 Physical activity, smoking status and risk of lung cancer ................... 375
23.3 Summary ...................................................................................................................... 376
23.4 Conclusion ................................................................................................................... 376
23.4.1 Hazard identification ................................................................................. 376
23.4.2 Risk assessment ........................................................................................... 376
23.6 Methodological quality of studies .......................................................................... 378
24 References .......................................................................................................................... 381
25 Appendices ........................................................................................................................ 413
25.1 Appendix A NHMRC Levels of Evidence19 – Aetiology ...................................... 413
25.2 Appendix B Search history ....................................................................................... 414
25.2.1 PubMed Cancer Lit .................................................................................... 414
25.2.2 Embase ......................................................................................................... 417
25.2.3 Lung Cancer search histories (minor databases) ................................ 420
JBI Library (1998 – 28/03/2011) ................................................................................. 420
Bandolier (1995 - 28/03/2011) .................................................................................. 420
Index to Theses (1970 – 29/03/2011) ....................................................................... 420
Fade: The Northwest Grey literature Service ........................................................ 420
The Networked digital library of Theses and Dissertations (1900-2012) ............ 421
Scirus ETD.. .................................................................................................................... 421
VTLS visualiser ............................................................................................................... 421
Australian Digital Theses ............................................................................................ 421
DART-Europe E-theses Portal .................................................................................... 421
25.3 Appendix C Critical appraisal instruments ........................................................... 422
25.3.1 JBI Critical Appraisal Checklist for Comparable Cohort/ Case
Control .......................................................................................................... 422
25.3.2 JBI Critical Appraisal Checklist for Systematic Reviews ...................... 423
25.4 Appendix D Excluded studies ................................................................................. 424
25.4.1 Risk factor – Asbestos ................................................................................. 424
25.4.2 Risk factor – Avian exposure .................................................................... 425
25.4.3 Risk factor – Red meat and processed meat consumption .............. 425
25.4.4 Risk factor – Family history ......................................................................... 426
25.4.5 Risk factor – Wood dust ............................................................................. 426
25.5 Appendix E Tables of included studies ................................................................. 428
25.5.1 Air Pollution .................................................................................................. 428
25.5.2 Alcohol Consumption ................................................................................ 432
25.5.3 Arsenic exposure ........................................................................................ 440
25.5.4 Asbestos ....................................................................................................... 445
25.5.5 Avian Exposure ........................................................................................... 453
25.5.6 Beryllium exposure ...................................................................................... 455
25.5.7 Cadmium ..................................................................................................... 459
25.5.8 Chromium IV ................................................................................................ 466
25.5.9 Dietary Cholesterol and Blood Cholesterol ........................................... 471
25.5.10 Family history ............................................................................................... 482
Risk factors for lung cancer: A systematic review xiv
25.5.11 Iron and Steel .............................................................................................. 483
25.5.12 Red Meat and Processed Meat Consumption .................................... 486
25.5.13 Nickel ............................................................................................................ 495
25.5.14 Polycyclic Aromatic Hydrocarbons (PAH) exposure ........................... 501
25.5.15 Painting as an occupation ....................................................................... 507
25.5.16 Physical Activity .......................................................................................... 511
25.5.17 Radon ........................................................................................................... 515
25.5.18 Silica .............................................................................................................. 527
25.5.19 Smoking: Active and passive smoking ................................................... 533
25.5.20 Wood Dust ................................................................................................... 540
Tables
Table 3.1 Summary of results of database searching, papers retrieved based on
eligibility criteria and number of included studies ..................................................... 16
Table 4.1 Study characteristics relevant to the association between smoking and
lung cancer ....................................................................................................................... 19
Table 4.2 Risk of lung cancer due to smoking in current and former smokers.
Referent category of never smokers31 ......................................................................... 26
Table 4.3 Differences in RR estimate of lung cancer in current smokers dependent
on the study design used31 ............................................................................................. 26
Table 4.4 Dose response RR estimates for lung cancer in current smoking men and
women31 ............................................................................................................................ 27
Table 4.5 Risk of lung cancer with workplace exposure to environmental tobacco
smoke32 .............................................................................................................................. 27
Table 4.6 Relative risk of lung cancer in never smoking men alone and both
genders when exposed to environmental smoke from their spouse33 .................. 28
Table 4.7 Second hand smoke (ETS) exposure during childhood and risk of lung
cancer34 ............................................................................................................................. 28
Table 4.8 Active smoking and passive smoking: Methodological quality of
included studies ............................................................................................................... 31
Table 5.1 Study characteristics relevant to the association between asbestos
exposure and lung cancer ............................................................................................ 36
Table 5.2 Risk estimates of lung cancer due to occupational asbestos exposure –
Mining worker cohort studies, IARC monograph 40 ................................................... 42
Table 5.3 Occupational asbestos exposure and risk estimates of lung cancer from
manufacturing worker cohort studies, IARC monograph40 unless
otherwise stated ............................................................................................................... 42
Table 5.4 Relative risk estimates of lung cancer due to occupational asbestos
exposure – Case controls with exposure measured in number of years,
IARC monograph40 .......................................................................................................... 45
Table 5.5 Case controls with exposure measured in number of hours, IARC
monograph40 .................................................................................................................... 46
Table 5.6 Risk estimates of lung cancer due to occupational asbestos exposure –
case-controls with categorical exposure, IARC monograph40 unless
otherwise stated ............................................................................................................... 47
Risk factors for lung cancer: A systematic review xvi
Table 5.7 Non-occupational asbestos exposure and risk of lung cancer, IARC
monograph40 .................................................................................................................... 49
Table 5.8 Asbestos exposure, gender and risk of lung cancer , IARC monograph40 ........... 50
Table 5.9 Occupational exposure to asbestos, smoking status and risk of lung
cancer ................................................................................................................................ 50
Table 5.10 Asbestosis and risk of lung cancer ................................................................................ 52
Table 5.11 Asbestos exposure: Methodological quality of included studies .......................... 56
Table 6.1 Study characteristics relevant to the association between radon
exposure and lung cancer ............................................................................................ 62
Table 6.2 Occupational radon exposure and risk of lung cancer in Europe (cohort
studies) ............................................................................................................................... 73
Table 6.3 Level of occupational radon exposure and risk of lung cancer in German
uranium miners, (Schnelzer et al. 2010)69 ..................................................................... 73
Table 6.4 Occupational radon exposure and risk of lung cancer in haematite/iron
miners, IARC monograph55 ............................................................................................ 74
Table 6.5 Occupational radon exposure and risk of lung cancer in Swedish iron ore
miners, (Jonsson et al. 2010) .......................................................................................... 74
Table 6.6 Occupational radon exposure, smoking and risk of lung cancer in miners,
IARC monograph 55 ......................................................................................................... 75
Table 6.7 Occupational radon exposure and risk of lung cancer in German
uranium miners: risk to smokers compared with non-smokers, (Schnelzer
et al. 2010)69 ...................................................................................................................... 75
Table 6.8 Occupational radon exposure, smoking status and risk of lung cancer in
German, French and Czech uranium miners, Leuraud et al. 201171 ..................... 75
Table 6.9 Residential radon exposure and risk of lung cancer, IARC monograph55 ........... 76
Table 6.10 Duration of residential radon exposure in Germany, (Kreutzer et al. 2003) 72 .......................................................................................................................................... 77
Table 6.11 Residential radon exposure and risk of lung cancer in the US, ( Krewski et
al. 2005)66 ........................................................................................................................... 77
Table 6.12 Residential radon exposure and lung cancer risk in China,(Lubin et al.
2004)73................................................................................................................................. 77
Table 6.13 Residential radon exposure and risk of lung cancer - a synthesis of data
from different exposure levels, (Pavia et al. 2003)75 .................................................. 78
Table 6.14 Residential radon exposure, smoking status and risk of lung cancer in
Sweden, (Lagarde et al. 2001) ...................................................................................... 78
Table 6.15 Residential radon exposure of 100 Bq/m3 for at least five years, smoking
status and risk of lung cancer, (Lubin et al. 2004) ..................................................... 79
Table 6.16 Residential radon exposure, gender and risk of lung cancer in Italy (Pisa
et al. 2001) ......................................................................................................................... 79
Table 6.17 Radon exposure: Methodological quality of included studies .............................. 82
Table 7.1 Study characteristics relevant to the association between arsenic
exposure and lung cancer ............................................................................................ 89
Table 7.2 Risk estimates for ever exposed versus non-exposed, before and after
adjustment for metals and other occupational exposures (‘t Mannetje et
al. 2011) .............................................................................................................................. 94
Table 7.3 Risk estimates for lung cancer according to exposure-response analyses
for arsenic dust and arsenic fumes/mist in terms of duration (years) (‘t
Mannetje et al. 2011) ...................................................................................................... 94
Table 7.4 Risk estimates of lung cancer due to occupational arsenic exposure –
Smelter studies; IARC monograph80 unless otherwise stated .................................. 96
Table 7.5 Risk estimates of lung cancer due to occupational arsenic exposure –
Mining studies, IARC monograph80 unless otherwise stated ................................... 99
Table 7.6 Risk of lung cancer, by occupation in smelters or mines ....................................... 102
Table 7.7 Risk estimates of lung cancer due to occupational arsenic exposure –
Fertilisation plant, stoking, pesticides and refinery studies, IARC
monograph80 unless otherwise stated ....................................................................... 103
Table 7.8 Risk estimates for lung cancer due to arsenic exposure among men living
near arsenic-emitting smelters, by smoking status (Pershagen et al. 1985) ....... 104
Table 7.9 Cumulative air arsenic exposure index* (CAAEI) in all male primary
smelter workers and in primary smelter workers who were current smokers
(Lundstrom et al. 2006) .................................................................................................. 105
Table 7.10 Age-adjusted relative risks for ever and current tobacco use in male tin
miners at high risk for lung cancer (Qiao et al. 1997) ............................................. 105
Table 7.11 Lung cancer mortality in male and female workers .............................................. 106
Table 7.12 Risk estimates of lung cancer due to arsenic exposure from drinking
water, IARC monograph 80 unless otherwise stated ............................................... 107
Table 7.13 Risk estimates for lung cancer mortality according to arsenic
concentration of well water, by smoking status (Tsuda et al. 1989) .................... 108
Risk factors for lung cancer: A systematic review xviii
Table 7.14 Risk of lung cancer and exposure to arsenic in drinking water by smoking
status ................................................................................................................................. 108
Table 7.15 Risk of lung cancer and exposure to arsenic in drinking water in males
and females, IARC monograph80 ............................................................................... 109
Table 7.16 Arsenic exposure: Methodological quality of included studies .............................. 112
Table 8.1 Study characteristics relevant to the association between PAH exposure
and lung cancer ............................................................................................................ 117
Table 8.2 Overall SMR and pooled RR with 95% CI for exposure to PAH in various
industries and occupations96 ....................................................................................... 123
Table 8.3 Risk estimates for lung cancer from occupational exposure to PAHs ................. 124
Table 8.4 Occupational exposure to PAHs and risk of lung cancer in coal
gasification workers ....................................................................................................... 126
Table 8.5 Occupational PAH exposure and risk of lung cancer in coke production
workers ............................................................................................................................. 127
Table 8.6 Occupational PAH exposure and risk of lung cancer in creosote workers.
(Tornqvist et al. 1986) ..................................................................................................... 128
Table 8.7 Occupational PAH exposure and risk of lung cancer in aluminium
production workers ........................................................................................................ 129
Table 8.8 Occupational PAH exposure, smoking status and risk estimates for lung
cancer .............................................................................................................................. 131
Table 8.9 Occupational PAH exposure, gender and hazard ratio and 95% CI for
lung cancer 103 ................................................................................................................ 131
Table 8.10 PAH exposure: Methodological quality of included studies ................................ 133
Table 9.1 Study characteristics relevant to the association between family history
and lung cancer ............................................................................................................ 137
Table 9.2 Pooled analysis of the overall risk of lung cancer associated with family
history114............................................................................................................................ 139
Table 9.3 Risk of lung cancer associated with family history, by smoking status –
and affected family member (case-control) ........................................................... 139
Table 9.4 Family history and the risk of lung cancer by gender,114 ........................................ 140
Table 9.5 Risk of lung cancer associated with family history, by family member
type, from the Lissowska et al. (2010) 114 case-control study ................................. 140
Table 9.6 Family history: Methodological quality of included studies .................................. 142
Table 10.1 Study characteristics relevant to the association between iron and steel
founding and lung cancer ........................................................................................... 145
Table 10.2 Iron and steel foundry workers and overall risk of lung cancer ............................ 148
Table 10.3 Risk estimates of lung cancer in iron and steel foundry workers, by
specific exposure to silica and formaldehyde124 ..................................................... 149
Table 10.4 Risk estimates of lung cancer in iron and steel foundry workers, by job
category .......................................................................................................................... 150
Table 10.5 Risk of lung cancer in iron and steel foundry workers, by duration of
employment, IARC monograph108 ............................................................................. 152
Table 10.6 Risk of lung cancer in iron and steel foundry workers, by smoking status........... 153
Table 10.7 Risk of lung cancer in iron and steel foundry workers; by gender and job,
(Ahn et al. 2010) ............................................................................................................. 154
Table 10.8 Iron and steel founding: Methodological quality of included studies ................ 156
Table 11.1 Study characteristics relevant to the association between silica exposure
and lung cancer ............................................................................................................ 160
Table 11.2 Overall risk of lung cancer associated with exposure to silica ............................. 167
Table 11.3 Risk estimates of lung cancer due to occupational silica exposure – Ore
mining; cohort & case-control studies, IARC Monograph (1997)128 ..................... 168
Table 11.4 Risk estimates of lung cancer due to occupational silica exposure –
Ceramics, pottery, refractory brick and diatomaceous earth; cohort &
case-control studies, IARC Monograph (1997)128 .................................................... 169
Table 11.5 Risk estimates of lung cancer due to occupational silica exposure –
Quarries and granite production and foundry workers; IARC Monograph
(1997)128 ............................................................................................................................ 170
Table 11.6 Duration of silica exposure and risk of lung cancer ................................................ 171
Table 11.7 Cumulative silica exposure and risk of lung cancer ............................................... 171
Table 11.8 Intensity of silica exposure and risk of lung cancer ................................................. 171
Table 11.9 Lung cancer risk associated with silica exposure in silicotic patients .................. 173
Table 11.10 Risk estimates of lung cancer due to occupational silica exposure in
silicotics, case-control studies, IARC Monograph (1997)128 ................................... 174
Table 11.11 Silica exposure, smoking status and risk of lung cancer135 .................................... 174
Table 11.12 Silica exposure: Methodological quality of included studies ............................... 176
Risk factors for lung cancer: A systematic review xx
Table 12.1 Study characteristics relevant to the association between nickel
exposure and lung cancer .......................................................................................... 181
Table 12.2 Occupational exposure to nickel and overall lung cancer risk; all studies
included in the IARC monograph139 except for where denoted......................... 187
Table 12.3 Duration of nickel exposure and risk of lung cancer .............................................. 188
Table 12.4 Cumulative exposure to water soluble nickel and Ni oxide and risk of lung
cancer; IARC 2012.139 .................................................................................................... 188
Table 12.5 Risk resulting from exposure to nickel and smoking status ..................................... 189
Table 12.6 Type of nickel compound and lung cancer risk, (Grimsrud et al. 2002) ............. 190
Table 12.7 Nickel exposure: Methodological quality of included studies .............................. 192
Table 13.1 Study characteristics relevant to the association between painting as an
occupation and lung cancer ..................................................................................... 196
Table 13.2 Overall lung cancer risk for painting as an occupation, any duration ............... 200
Table 13.3 Lung cancer risk for exposure to wood and gypsum paints,
(Ramanakumar et al. 2011)157 ..................................................................................... 202
Table 13.4 RR of lung cancer and occupational exposure to paint by duration of
employment, (Guha et al. 2010)153 ............................................................................ 202
Table 13.5 Lung cancer risk for general painting work (not spraying) and spray
painting in Chinese non-smoking men by duration of employment (Tse et
al. 2011) ............................................................................................................................ 202
Table 13.6 Lung cancer risk for painting as an occupation and exposure to wood
and gypsum paints by duration of employment157................................................. 203
Table 13.7 Lung cancer risk for painting as an occupation by gender153 ............................. 203
Table 13.8 Painting as an occupation: Methodological quality of included studies .......... 206
Table 14.1 Study characteristics relevant to the association between cadmium
exposure and lung cancer .......................................................................................... 211
Table 14.2 Risk estimates of lung cancer due to occupational cadmium exposure;
research synthesis148 ...................................................................................................... 215
Table 14.3 Risk estimates of lung cancer due to occupational exposure to
cadmium, case-control study (t Mannetje et al. 2011)92 ....................................... 215
Table 14.4 Risk estimates of lung cancer due to occupational cadmium exposure,
cohort studies – IARC monograph160 ......................................................................... 216
Table 14.5 Duration of occupational cadmium exposure and risk of lung cancer ............. 220
Table 14.6 Risk of lung cancer resulting from occupational cadmium exposure by
weighted duration or cumulative exposure (t Mannetje et al. 2011)92 ............... 220
Table 14.7 Risk of lung cancer from occupational cadmium exposure, by exposure
intensity ............................................................................................................................ 221
Table 14.8 Residential cadmium exposure and risk of lung cancer ........................................ 222
Table 14.9 Risk of lung cancer resulting from any level of cadmium exposure in non-
smokers vs smokers ........................................................................................................ 222
Table 14.10 Cadmium exposure: Methodological quality of included studies ...................... 225
Table 15.1 Study characteristics relevant to the association between air pollution
and lung cancer ............................................................................................................ 230
Table 15.2 Risk of lung cancer associated with exposure to fine particulate matter
(PM2.5) ............................................................................................................................. 235
Table 15.3 Risk of lung cancer associated with exposure to fine particulate matter
(PM2.5) and gender, (Chen et al.)188 ......................................................................... 236
Table 15.4 Sulphur dioxide (SO2) exposure and risk of lung cancer ........................................ 236
Table 15.5 Risk of lung cancer associated with exposure to sulphur dioxide (SO2)
and gender, (Chen et al. 2008) .................................................................................. 236
Table 15.6 Risk of lung cancer associated with exposure to nitrogen dioxide (NO2) .......... 237
Table 15.7 Risk of lung cancer associated with exposure to nitrogen oxides (NOx) ........... 237
Table 15.8 Risk of lung cancer associated with a 20yr exposure to nitrogen oxides
(NOx) and smoking status, (Raaschou-Nielsen et al.)194 ........................................ 238
Table 15.9 Risk of lung cancer associated with a 20 yr exposure to nitrogen oxides
(NOx) and gender, (Raaschou-Nielsen et al.)194 ..................................................... 238
Table 15.10 Risk of lung cancer associated with exposure to vehicular traffic ....................... 238
Table 15.11 Risk of lung cancer associated with exposure to vehicular traffic and
smoking status195............................................................................................................. 239
Table 15.12 Air pollution: Methodological quality of included studies ..................................... 242
Table 16.1 Study characteristics relevant to the association between chromium (VI)
exposure and lung cancer .......................................................................................... 246
Table 16.2 Risk estimates of lung cancer due to occupational Cr VI exposure,
research syntheses ......................................................................................................... 251
Table 16.3 Risk estimates of lung cancer due to occupational Cr VI exposure,
cohort studies - IARC monograph (2012f) and Hara et al. (2010) ........................ 252
Risk factors for lung cancer: A systematic review xxii
Table 16.4 Lung cancer risk resulting from occupational Cr VI exposure - by duration ...... 253
Table 16.5 Risk of lung cancer resulting from occupational Cr VI exposure by
weighted duration or cumulative exposure, (‘t Mannetje et al 2011) ................ 253
Table 16.6 Risk of lung cancer resulting from occupational Cr VI exposure, 211 211 .............. 254
Table 16.7 Overall risk of lung cancer resulting from occupational Cr VI exposure
and smoking,148 .............................................................................................................. 254
Table 16.8 Chromium exposure: Methodological quality of included studies ..................... 256
Table 17.1 Study characteristics relevant to the association between beryllium
exposure and lung cancer .......................................................................................... 261
Table 17.2 Occupational beryllium exposure and overall risk of lung cancer ...................... 267
Table 17.3 Quantified levels of occupational beryllium exposure and overall risk of
lung cancer ..................................................................................................................... 269
Table 17.4 SMRs for lung cancer in US male beryllium workers employed 1940-1969
by latency and employment duration (Ward et al. 1992) .................................... 270
Table 17.5 Lung cancer risk estimates by cumulative occupational beryllium
exposure, (Sanderson et al. 2001)............................................................................... 270
Table 17.6 Lung cancer risk estimates by cumulative occupational beryllium
exposure (lagged 10 years), Schubauer-Berigan et al (2011a) ............................ 271
Table 17.7 Beryllium exposure: Methodological quality of included studies ........................ 273
Table 18.1 Study characteristics relevant to the association between red/processed
meat consumption and lung cancer ........................................................................ 277
Table 18.2 Red meat consumption, smoking status and risk of lung cancer ........................ 287
Table 18.3 Risk of lung cancer with processed meat consumption by smoking status
(De Stefani et al. 2009) .................................................................................................. 289
Table 18.4 Risk of lung cancer with processed meat consumption for women ................... 290
Table 18.5 Red and processed meat consumption: Methodological quality of
included studies ............................................................................................................. 292
Table 19.1 Study characteristics relevant to the association between alcohol
consumption and lung cancer ................................................................................... 298
Table 19.2 Risk of lung cancer incidence in general population by lowest and
highest alcohol intake categories .............................................................................. 307
Table 19.3 Risk ratios for alcohol consumption and lung cancer risk in non-smokers
(Korte et al. 2002) ........................................................................................................... 307
Table 19.4 Multivariate adjusted Hazard ratio for lung cancer incidence by smoking
status (Shimazu et al 2008) ........................................................................................... 307
Table 19.5 Relative risk of lung cancer in women by smoking status (Rachtan &
Sokolowski 1997) ............................................................................................................. 308
Table 19.6 Odds ratio for alcohol consumption and lung cancer risk by smoking
status (Pierce et al 1989) ............................................................................................... 308
Table 19.7 Binge drinking and risk of lung cancer according to smoking status
(Toriola et al 2009) .......................................................................................................... 308
Table 19.8 Relative risk of lung cancer among binge drinkers compared with non-
binge drinkers in men with no history of lung cancer at baseline (Toriola
et al 2009) ........................................................................................................................ 309
Table 19.9 Increased risk of lung cancer in men with increasing amount of alcohol
(Balder et al 2009) .......................................................................................................... 309
Table 19.10 Risk of lung cancer with consumption of vodka in women (Rachtan et al
1997) ................................................................................................................................. 309
Table 19.11 Relative risk for alcoholic beverage types and lung cancer risk (Chao et
al. 2007) ............................................................................................................................ 310
Table 19.12 Odds ratio for beer consumption and risk of lung cancer (Mayne et al.
1994) ................................................................................................................................. 310
Table 19.13 Alcohol consumption: Methodological quality of included studies ................... 313
Table 20.1 Study characteristics relevant to the association between cholesterol
and lung cancer ............................................................................................................ 319
Table 20.2 Risk of lung cancer and dietary cholesterol intake in quartiles of
consumption ................................................................................................................... 328
Table 20.3 Pooled multivariate-adjusted RRs and 95% CIs of lung cancer for dietary
cholesterol (for 100mg/day increases), (Smith Warner et al. 2002) ..................... 328
Table 20.4 RRs and 95% CIs of lung cancer by smoking status according to quartile
intake of dietary cholesterol among postmenopausal women (Wu et al.
1994) ................................................................................................................................. 329
Table 20.5 ORs and 95% CIs for the development of lung cancer among males, by
quartiles of cholesterol consumption, (Goodman et al. 1988) ............................. 329
Table 20.6 ORs and 95% CIs for lung cancer risk with highest quartile of cholesterol
intake compared to other quartiles in men, (Steenland et al. 1995) .................. 330
Table 20.7 Risk of lung cancer and dietary cholesterol consumption in quartiles ............... 330
Risk factors for lung cancer: A systematic review xxiv
Table 20.8 Risk of lung cancer and dietary cholesterol consumption in tertiles for
men. No CIs reported, (Shekelle et al. 1991) ............................................................ 330
Table 20.9 Risk of lung cancer and dietary cholesterol consumption in women in
quintiles ............................................................................................................................ 331
Table 20.10 Risk of lung cancer and dietary cholesterol consumption in quartiles ............... 331
Table 20.11 ORs and 95% CIs for lung cancer risk with highest quartile of cholesterol
intake compared to other quartiles in women (Steenland et al. 1995) .............. 331
Table 20.12 RRs and 95% CIs of lung cancer in relation to serum total cholesterol
(mg/dL) in quintiles (Ahn et al. 2009) ......................................................................... 332
Table 20.13 Association of plasma HDL-cholesterol quartiles with incidence of lung
cancer (RRs & 95% CIs) (Kucharska-Newton et al. 2008) ....................................... 332
Table 20.14 Lung cancer risk and serum cholesterol level (Keys et al. 1985) .......................... 333
Table 20.15 Relative Hazards and 95% CIs of lung cancer mortality by low plasma
cholesterol (
Table 22.6 Lung cancer risk among pulp and paper industry workers exposed to
wood dust by cumulative dose (Szadkowska-Stanczyk & Szymczak 2001) ....... 362
Table 22.7 Wood dust: Methodological quality of included studies ...................................... 364
Table 23.1 Study characteristics relevant to the association between physical
activity and lung cancer .............................................................................................. 368
Table 23.2 Leisure time physical activity (LPA) and lung cancer (Tardon et al. 2005) ........ 372
Table 23.3 Relative Risk of lung cancer at different levels of physical activity (Lee et
al. 1994) ............................................................................................................................ 372
Table 23.4 Relative Risk of lung cancer according to frequency of physical
activity/week (Leitzmann et al. 2009) ........................................................................ 373
Table 23.5 Lung cancer risk in women with different measures of leisure time
physical activity (LPA) (Sinner et al. 2006) ................................................................. 373
Table 23.6 Incident rate ratios (IRR) for lung cancer in relation to categories
according to time spent on each of the different types of physical
activity in leisure time (Bak et al. 2005) ...................................................................... 374
Table 23.7 Risk of lung cancer by type of physical activity (PA) and by gender
(Steindorf et al. 2006) .................................................................................................... 374
Table 23.8 Physical activity: Methodological quality of included studies ............................. 378
Risk factors for lung cancer: A systematic review xxvi
Figures
Figure 5.1 Meta-analysis of effect estimates of cohort studies presenting risk of lung
cancer with occupational exposure in crocidolite miners, IARC
monograph40 .................................................................................................................... 41
Figure 5.2 Meta-analysis of effect estimates of cohort studies presenting risk of lung
cancer with occupational exposure in manufacturing workers, IARC
monograph40 .................................................................................................................... 44
Figure 5.3 Meta-analysis of effect estimates of cohort studies presenting risk of lung
cancer with occupational exposure in shipyard, rail yard workers and
plumbers, IARC monograph40 ....................................................................................... 44
Figure 5.4 Meta-analysis of effect estimates of case control studies presenting risk of
lung cancer with occupational exposure to asbestos (a) < 7-10 years, (b)
> 8-10 years. ...................................................................................................................... 47
Figure 8.1 Occupational exposure to PAHs and risk of lung cancer, by longest
duration of exposure (≥30 years) ................................................................................ 125
Figure 8.2 Occupational exposure to PAHs and risk of lung cancer in coal
gasification workers ....................................................................................................... 126
Figure 8.3 Occupational cumulative PAH exposure (BaP) and risk of lung cancer in
aluminium production workers .................................................................................... 129
Figure 8.4 Occupational PAH exposure and risk of lung cancer in chimney sweeps
and in workers exposed to soot .................................................................................. 130
Figure 10.1 Iron and steel foundry workers and overall risk of lung cancer ............................ 149
Figure 10.2 Risk of lung cancer in iron and steel foundry workers employed for more
than 30 years ................................................................................................................... 151
Figure 10.3 Risk of lung cancer in iron and steel foundry workers employed for less
than 10 years ................................................................................................................... 152
Figure 11.1 Overall risk of lung cancer due to occupational silica exposure in workers
in ore mining industry ..................................................................................................... 168
Figure 11.2 Risk estimates of lung cancer due to occupational silica exposure in
workers in Ceramics, Pottery and Diatomaceous earth industries ...................... 169
Figure 18.1 Meta-analysis of risk of lung cancer with red meat consumption including
all cohorts ........................................................................................................................ 285
Figure 18.2 Risk of lung cancer associated with red meat consumption for men ................ 287
Figure 18.3 Red meat consumption and risk of lung cancer in women .................................. 288
Figure 18.4 Meta-analysis of risk of lung cancer with processed meat consumption in
11 included cohorts ....................................................................................................... 289
Figure 18.5 Risk of lung cancer with processed meat consumption for men ......................... 290
Figure 19.1 Meta-analysis of risk of lung cancer (RR) in individuals with high alcohol
consumption ................................................................................................................... 306
Figure 19.2 Risk of lung cancer among alcoholic male and female patients ....................... 311
Figure 20.1 Risk of lung cancer and dietary cholesterol intake by highest tertile of
consumption in men ...................................................................................................... 329
Figure 21.1 Meta-analysis of risk of lung cancer (RR) and avian exposure ............................. 345
Figure 21.2 Meta-analysis of risk of lung cancer (RR) in never smoking women from
avian exposure .............................................................................................