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78 and gender, there was a significant trend in risk with increasing amounts smoked per week by the spouse (P = 0.05) and with cumulative pack-years of exposure (P = 0.03). This effect was limited to females, especially older women whose husbands were heavy smokers. The elevated risk associated with spouse smoking was restricted to squamous and small cell carcinomas (odds ratio, 2.9; 95% con- fidence interval, 0.9-9.3), which provides additional evidence linking pas- sive smoking to lung cancer. Quantification of the Lung Cancer Risk From Radon Daughter Exposure in Dwellings - An Epidemiological Approach. Edling, C., Wingren, G., Axelson, O. Department of Occupational Medicine, University Hospital, S-581 85 Linkoping, Sweden. Environ. Int. 12: 55-60, 1986. Some epidemiological studies have suggested a relationship Detween the con- centration of decay products from radon, i.e., radon daughter exposure, in dwell- ings and lung cancer. Further experiences made from radon measurements have indi- cated that both building material and particularly the radioactivity in the ground is of importance for the leakage of radon into the houses. In Sweden, a survey is now ongoing in 15 municipalities with alum shale deposits, and in one area a case-referent evalua- tion has been made, considering building materials, ground conditions and smoking habits. The size of the study is small, but the results suggest that a risk is at hand and that there is a multiplicative effect from smoking and radon daughter exposure. About 30% of the lung cancers in the studied population might be at- tributable to elevated and potentially avoidable exposure to radon and radon daughters. Models for Respiratory Cancer in Nickel Refinery Workers. Kaldor, J., Peto, J., Easton, D. et al. Unit of Biostatistics and Field Studies, Division of Epidemiology and Biostatistics, International Agency for Research on Cancer, 69372 Lyon Cedex 08, France. J. Natl. Cancer Inst. 77: 841- 848, 1986. Lung and nasal sinus cancer death rates among employees of a nickel refinery in South Wales were examined from the standpoint of quantifying the relationship between exposure and the risk of these two cancers. Areas in the refinery associated with high risk were identified by using a matched case- control approach, and a simple index of exposure for each man was constructed ac- cordingly based on the duration of time spent in these areas. The dependence of relative risk and absolute excess risk for lung and nasal sinus cancers on age at first employment, calendar period of first employment, time since first employment, and duration of exposure in high-risk areas was then analyzed. The relative risk for nasal sinus cancer in- creased sharply with increasing age at first exposure but remained roughly con- stant throughout the period of follow-up, while that for ~ung cancer was indepen- dent of age at first exposure and dropped sharply with increasing time since first employment. The implications and limita- tions of these analyses are discussed in relation to the multistage theory of car- cinogenesis and occupational risk assessment. Silica Dust and Lung Cancer: Results From the Nordic Occupational Mortality and Cancer Incidence Registers. Lynge, E., Kurppa, K., Kristoffersen, L. et al. Danish Cancer Registry, DK-2100 Copenhagen O, Denmark. J. Natl. Cancer Inst. 77: 883-889, 1986. Autopsy studies of the relationship between silicosis and lung cancer have been mainly negative; but recent epidemiologic studies have indicated a positive association, and an excess lung cancer risk has been observed in some oc- cupational groups with exposure to silica dust. For the further shedding of light on the possible association between silica dust and lung cancer, analysis was made on mortality and cancer incidence data available in census-based record linkage studies from the Nordic countries for males in occupational groups with potential exposure to silica dust. The study showed an excess lung cancer risk for foundry workers in all the Nordic countries and for miners in Sweden. These results were consistent with findings from previous in-depth epidemiologic studies. The lung cancer risk did not differ significantly from that of the respective national populations for males working in excavation; stone quarries; sand and gravel pits; and glass, porcelain, ceramic, and tile manufacture. Stonecutters, who are probably not ex- posed to known lung carcinogens at the workplace but in some places to high con- centrations of silica dust, showed a sig- nificant excess lung cancer risk in both Finland and Denmark. Excess lung cancer risks furthermore were seen for Finnish miners, for Finnish males in excavation work, and for Danish glassworkers. Silicosis and Risk of Lung Cancer or Lung Tuberculosis: A Cohort Study. Westerholm, P., Ahlmark, A., Maasing, R., Segelberg, I. Swedish Confederation of Trade Unions, S-105 53 Stockholm, Sweden. Environ. Res. 41: 339-350, 1986. This is a study of cancer mortality, cancer incidence, and incidence of lung tuberculosis among cases of silicosis reported to the National Swedish Pneumoconiosis Register during 1959-1977. Two occupational categories were ex- tracted - 'mining, tunneling, and

Silicosis and risk of lung cancer or lung tuberculosis: A cohort study

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78

and gender, there was a significant trend in risk with increasing amounts smoked per week by the spouse (P = 0.05) and with cumulative pack-years of exposure (P = 0.03). This effect was limited to females, especially older women whose husbands were heavy smokers. The elevated risk associated with spouse smoking was restricted to squamous and small cell carcinomas (odds ratio, 2.9; 95% con- fidence interval, 0.9-9.3), which provides additional evidence linking pas- sive smoking to lung cancer.

Quantification of the Lung Cancer Risk From Radon Daughter Exposure in Dwellings - An Epidemiological Approach. Edling, C., Wingren, G., Axelson, O. Department of Occupational Medicine, University Hospital, S-581 85 Linkoping, Sweden. Environ. Int. 12: 55-60, 1986.

Some epidemiological studies have suggested a relationship Detween the con- centration of decay products from radon, i.e., radon daughter exposure, in dwell- ings and lung cancer. Further experiences made from radon measurements have indi- cated that both building material and particularly the radioactivity in the ground is of importance for the leakage of radon into the houses. In Sweden, a survey is now ongoing in 15 municipalities with alum shale deposits, and in one area a case-referent evalua- tion has been made, considering building materials, ground conditions and smoking habits. The size of the study is small, but the results suggest that a risk is at hand and that there is a multiplicative effect from smoking and radon daughter exposure. About 30% of the lung cancers in the studied population might be at- tributable to elevated and potentially avoidable exposure to radon and radon daughters.

Models for Respiratory Cancer in Nickel Refinery Workers. Kaldor, J., Peto, J., Easton, D. et al. Unit of Biostatistics and Field Studies, Division of Epidemiology and Biostatistics, International Agency for Research on Cancer, 69372 Lyon Cedex 08, France. J. Natl. Cancer Inst. 77: 841- 848, 1986.

Lung and nasal sinus cancer death rates among employees of a nickel refinery in South Wales were examined from the standpoint of quantifying the relationship between exposure and the risk of these two cancers. Areas in the refinery associated with high risk were identified by using a matched case- control approach, and a simple index of exposure for each man was constructed ac- cordingly based on the duration of time spent in these areas. The dependence of relative risk and absolute excess risk for lung and nasal sinus cancers on age at first employment, calendar period of first employment, time since first

employment, and duration of exposure in high-risk areas was then analyzed. The relative risk for nasal sinus cancer in- creased sharply with increasing age at first exposure but remained roughly con- stant throughout the period of follow-up, while that for ~ung cancer was indepen- dent of age at first exposure and dropped sharply with increasing time since first employment. The implications and limita- tions of these analyses are discussed in relation to the multistage theory of car- cinogenesis and occupational risk assessment.

Silica Dust and Lung Cancer: Results From the Nordic Occupational Mortality and Cancer Incidence Registers. Lynge, E., Kurppa, K., Kristoffersen, L. et al. Danish Cancer Registry, DK-2100 Copenhagen O, Denmark. J. Natl. Cancer Inst. 77: 883-889, 1986.

Autopsy studies of the relationship between silicosis and lung cancer have been mainly negative; but recent epidemiologic studies have indicated a positive association, and an excess lung cancer risk has been observed in some oc- cupational groups with exposure to silica dust. For the further shedding of light on the possible association between silica dust and lung cancer, analysis was made on mortality and cancer incidence data available in census-based record linkage studies from the Nordic countries for males in occupational groups with potential exposure to silica dust. The study showed an excess lung cancer risk for foundry workers in all the Nordic countries and for miners in Sweden. These results were consistent with findings from previous in-depth epidemiologic studies. The lung cancer risk did not differ significantly from that of the respective national populations for males working in excavation; stone quarries; sand and gravel pits; and glass, porcelain, ceramic, and tile manufacture. Stonecutters, who are probably not ex- posed to known lung carcinogens at the workplace but in some places to high con- centrations of silica dust, showed a sig- nificant excess lung cancer risk in both Finland and Denmark. Excess lung cancer risks furthermore were seen for Finnish miners, for Finnish males in excavation work, and for Danish glassworkers.

Silicosis and Risk of Lung Cancer or Lung Tuberculosis: A Cohort Study. Westerholm, P., Ahlmark, A., Maasing, R., Segelberg, I. Swedish Confederation of Trade Unions, S-105 53 Stockholm, Sweden. Environ. Res. 41: 339-350, 1986.

This is a study of cancer mortality, cancer incidence, and incidence of lung tuberculosis among cases of silicosis reported to the National Swedish Pneumoconiosis Register during 1959-1977. Two occupational categories were ex- tracted - 'mining, tunneling, and

79

quarrying' (n = 284) and 'iron and steel foundries' (n = 428), respectively. Con- trol groups were drawn from a national register of persons undergoing periodic health examinations with regard to silicosis risk. The controls were matched for occupation, age, and time of first exposure. The follow-up was performed through record-linkage operations to com- puterized information in Swedish Death Statistics, Swedish Cancer Register, and the Swedish Tuberculosis Index. End of follow-up was set at December 31, 1980. In cases drawn from mining, quarrying, and tunneling workers seven deaths in lung cancer were observed and two among the controls. Among iron and steel foundry workers the corresponding numbers were i0 and 6. The values for expected numbers, based on general population statistics, were 1.3 and 2.6, respectively, for these two occupational groups. When cancer incidence statistics were used, the case/control ratio for lung cancer was 2.1 for 'mining, quarrying, tunneling' and 0.6 for 'iron and steel foundries'. There were 29 cases of lung tuberculosis registered among the silicosis cases during the follow-up period. Only one tuberculosis case was observed among the controls. The results demonstrate that persons with silicosis contracted in the mining, quarrying, and tunneling occupations are subject to an increased risk of lung cancer. The risk is observed when both the general popula- tion and a closely matched control population from the same occupations are used for values of reference. The results also demonstrate the high risk of persons with silicosis to contract lung tuberculosis.

No Association Between HLA Antigens and Adenocarcinoma of the Lung in Non-Smoking Chinese Women in Hong Kong. Lam, W.K., Hawkins, B.R., Kung, I.T.M., So, S.Y. Department of Medicine, Univer- sity of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong. Br. J. Dis. Chest 80: 370-374, 1986.

A high incidence rate of lung cancer with preponderance of adenocarcinoma in non-smokers has been reported in women of southern Chinese ethnic origin. Thirty- three southern Chinese female patients with primary adenocarcinoma of the lung, all lifelong non-smokers, were typed for HLA-A and B antigens to study the pos- sibility of genetically determined sus- ceptibility factors. The antigen frequencies were compared with those of ii0 healthy controls. No significant dif- ference in antigen frequencies was found in the patients compared with controls. Studies on other possible factors deter- mining susceptibility to lung cancer in Chinese women are necessary.

Endobronchial Carcinogenesis in Dog. Benfield, J.R.0 Hammond, W.G., Paladugu, R.R. et al. Department of Thoracic Surgery, City of Hope National Medical Center, Duarte, CA 91010, U.S.A. J. Thorac. Cardiovasc. Surg. 92: 880-889, 1986.

A canine model of squamous cell lung cancer has been developed through studies with ii0 dogs exposed by ii focal en- dobronchial regimens to chemical carcinogens: benzo(a)pyrene, nitrosomethylurea, methylcholanthrene, and dimethylbenzanthracene. A combination of nitrosomethylurea and benz(a)pyrene caused the first invasive cancer after 5.5 years. Toxic side-effects resulted from either nitrosomethylurea or high- dose dimethylbenzanthracene given by bronchial submucosal injection and from adjuvant immunosuppression with azathioprine and corticosteroids. Four regimens in 58 dogs caused 31 cancers, including five TI-2 N0 M0 cancers, 17 metastasizing carcinomas, and nine car- cinomas of elsser stages. The following regimens caused cancers: (i) sequential benzo(a)pyrene, nitrosomethylurea, and yttrium 91; (2) benzo(a)pyrene and topi- cal nitrosomethylurea; (3) low-dose dimethylbenzanthracene; (4) high-dose methylcholanthrene. The most suitable regimen to date has been 30 mg of methyl- cholanthrene given by submucosal injec- tion every 2 to 3 weeks; this produced cancers at preselected sites within 2 years of first exposure in eight of 10 dogs. The neoplastic continuum has fol- lowed a predictable, reproducible sequence that regularly began with epithelial hyperplasia. Squamous metaplasia occurred in 6 to 18 weeks; it was followed by progressive squamous atypia. The interval until invasive can- cer developed varied with the regimen employed; it was about 20 months with methylcholanthrene. Serial cytologic specimens, studied by image analysis, revealed progressive increase in mean to- tal cellular deoxyribonucleic acid con- tent from diploid in normal cells to greater than tetraploid in cancer cells (p < 0.01). We have recently been successful with serial passage of four canine lung cancers from four to twelve transplant generations in nude mice. There is now a predictable large animal model of squamous cell lung carcinoma at preselected site(s) that closely resembles human lung cancer. The preneoplastic period is short enough to be fiscally defensible, but long enough to permit study of the biologic changes during endobronchial carcinogenesis.