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+ RELATIONSHIP OF PASSIVE SMOKING AND PULMONARY ADENOCARCINOMA IN NON-SMOKING WOMEN -- A CASE-CONTROL STUDY IN NANJING By Shen, X.B.; Wang, G.X.; Zhou, X.P.; Wang, X.H. Nanjing Railway Medical College Nanjing, China Abstract: To examine the relationship between exposure to passive smoke, cooking fumes, other risk factors and primary adenocarcinoma of the lung, 70 adenocarcinoma lung cancer cases involving non-smoking women in Nanjing were studied in a 1:1 case-control study. Results show no statistical association between passive smoking and pulmonary adenocarcinoma. The respective RRs for chronic lung disease, cooking fume pollution and family tumor history were 3.90, 2.45, and 4.36. Key Words: Passive smoking, lung cancer, cooking fume. Introduction Ever since Hirayama and 'I'richopoulosl,2 first pepoTted on the relationship between exposure to passive smoke anct lun.g cane-er in 1981, many studies on the subject have appeared in various parts of the world with very different conclusions. Some have conc3.uded that passive smoking is related to lung cancer3,4,5, while others have found no association between the two6,7. Some investigators suggest that passive smoking is associated with soine, rather than

all, histologic types of lung cancers. To examine the relationship between passive smoking and female lung adenocarcinoma, a case- control study involving 70 cases of primary lung carcinoma in never-smoking females was performed. Materials and Methods Case Selection: In 1993, 70 cases of female non-smokers with primary lung cancer were identified (by International Classification of Disease Code 163) in Nanjing. The cases were required to have lived in Nanjing for at least 20 years. Control Selection: Healthy controls were randomly selected from the same neighborhoods and were matched 1:1 by sex, age (± 5 years) and occupation. Data Collection: A standardized questionnaire was used by trained medical staff to collect data on exposure to passive smoke, as well as other parameters from controls and cases. The data covered a period of 20 years, dating back from the day when lung adenocarcinoma was diagnosed. Data Analyses: 1) The Mantel-Haenszel method9 was used to analyze the relationship between exposure to environmental tobacco smoke (ETS) and pulmonary adenocarcinoma. The relationship between ETS - 2 - ~~

exposure levels and years of exposure and lung cancer was also analyzed. 2) Single-factor and multi-variate analyses of the coded data were performed by conditional logistic regression (Table 1). Table 1. Variables and Coding System for Conditional Logistic Regression Analysis Variables >:Codes Xl ETS exposure ENCY/20 N: number of family smoker C: cigarettes smoked per day for every smoker Y: smoking years for every smoker X2 Chronic lung diseases 0: none; 1: yes (Chronic bronchitis and pulmonary tuberculosis) X3 Living quarters condition average areas per person (m2) X4 Type of fuel in the home 0: gaseous fuel; 1: yes X5 Coal stove for heating 0: none; 1: yes X6 Cooking fume/pollution 0: none; 1: yes X7 Participation in cooking number of times per week X8 Family history of cancer 0: none; 1: yes Result 1. Analysis of the relationship between ETS and the occurrence of primary lung adenocarcinoma in non-smoking women. - 3 -

Table 2 is a comparison of ETS exposure in both cases and controls. XZM1{ = 0.7619, P> 0.05. Table 3 is a comparison of daily exposure to ETS. According to Mantel-Haenszel test of uniformity XzMH - 0.0800, P> 0.05. Table 4 is a comparison of the effects of years of ETS exposure in cases and controls. 2 X MH ~ 0.0120, P> 0.05. The results of all three comparisons show that there was no statistically significant association between ETS and pulmonary adenocarcinoma in this group of non-smoking women in Nanjing. Table 2. ETS Exposure and Non-Smoking Female Lung Adenocarcinoma cases yes no total controls yes 43 8 51 no 13 6 19 total 56 XZMf1 = 0.7619 P> 0. 0 5 14 70 Table 3. ETS Exposure and Non-smoking Female Lung Adenocarcinoma. ETS Exposure (Cigarettes Per Day) Cases Controls RR 95% Exposure 0 14 11 1.0 5 10 12 0.84 0.27-2.64 10 12 9 1.24 0.39-3.90 >20 34 38 0.85 0.26-2.74 XZMF1 = 0.0800 P > 0.05 - 4 -

Table 4. Years of ETS Exposure and Non-Smoking Female Lung Adenocaroinoma. Years of ETS Exposure Cases Controls RR 95% CI 0 14 11 1.0 10 19 24 0.80 0.30-2.12 >20 37 35 0.98 0.41-2.38 X2 M14 = 0.0120 P > 0.05 2. Conditional Logistic Regression Analyses. Table 5 is a conditional logistic regression single- factor analysis which shows that passive smoking was not statistically significantly associated with adenocarcinoma. Among the 8 variables, chronic lung disease, cooking fume pollution, and family tumor history show statistical significance. These three variables were then subjected to multi-variate analysis. These results are presented in Table 6. They show that the occurrence of lung adenocarcinoma in female non-smokers in Nanjing was related to kitchen cooking fume pollution, chronic lung disease and family history of tumor, with respective RRs of 3.90, 2.45, and 4.36. - 5 -

Table 5. Results of Single-Factor by Conditional Logistic Regression Standard Error of Regression Regression Coefficient Relative Risk Variables Coefficient (B) (SeB) (RR) 95% CI of RR P Value X1 0.3184 0.4646 1.38 0.55-3.42 0.2466 X2 1.8718 0.7594 6.50 1.47-28.80 0.0069 X3 0.0226 0.0305 1.08 0.96-1.09 0.2297 X4 0.4094 0.5888 1.51 0.47-4.78 0.2435 X5 0.5735 0.4166 1.78 0.79-4.02 0.0837 X6 1.2528 0.4009 3.50 1.60-7.68 0.0009 X7 0.0660 0.1041 1.07 0.87-1.31 0.2630 X8 1.8819 0.7602 6.60 1.48-29.13 0.0059 Table 6. Multi-variate Analysis by Conditional Logistic Regression Standard Error of Regression Regression Coefficient Relative Risk Variables Coefficient (B) (SeB) (RR) 95% CI of RR P Value X2 1.5245 0.7740 3.90 1.00-20.94 0.4785 X6 0.8941 0.4286 2.45 1.06-5.66 0.0185 X8 1.6012 0.8014 4.36 1.03-23.85 0.0354 Discussion The biological effects of exposure to ETS are complex; a major problem being how its effects can be accurately assessed. The effect of ETS exposure is not only related to the number of smokers and how much they smoke, but also their smoking habits, type of tobacco used and ventilation of living quarters. This survey was conducted by two groups of data takers at different times. The response rate was 100%, thereby assuring the accuracy and reliability of the data. - 6 -

The association of passive smoking and lung adeno- carcinoma has been reported by some in the literature.5,10 Our study, however, did not find an association. Whether by simple yes or no answer to exposure, or by the extent of daily exposure or years of exposure, no relationship was found between the two. Thus, the relation of ETS and lung adenocarcinoma, if any, is not supported by this study. By multi-variate analysis, the occurrence of pulmonary adenocarcinoma in non-smoking women of Nanjing was found to be associated with chronic lung disease, kitchen cooking fume pollution and family tumor history. It is known that Chinese women have low smoking rates yet high lung cancer rates, especially lung adenocarcinoma. Because of the custom of cooking with high heat in China, cooking fume is often an indoor pollutant. Air pollution due to cooking fumes should be noted by all. References 1. Hirayama, T. "Non-smoking Wives of Heavy Smokers Have a Higher Risk of Lung Cancer: A Study from Japan," Br. Med. J. 282: 183-185, 1981. 2. 'rrichopoulos, D., Kalandidi, A., Sparros, L., et al. "Lung Cancer and Passive Smoking," Int. J. Cancer 27: 1-4, 1981. - 7 -

3. Wynder, E.L., Goodman, M.T.. "Smoking and Lung Cancer: Some Unresolved Issues," Epidemiologic Review 5: 133-207, 1983. 4. Pershagen, G., Hrubec, Z., Svensson C. "Passive Smoking and Lung Cancer in Swedish Women," American J. of Epidemiology 125(1): 17-24, 1987. 5. Brownson, R.C., Reif, J.S., et al. "Risk Factors for Adenocarcinoma of the Lung," American J. of Epidemiology 125(1): 25-34. 6. Lee, P.N., Chamberlain, et al. "Relationship of Passive smoking to Risk of Lung Cancer and Other Smoking Associated Diseases," Br. J. Cancer 54: 97-105, 1986. 7. Williams A.H.W., Dai, X.D., Blot, W., et al. "Lung Cancer k Among Women in North-East China," Br. J. Cancer 62: 982-987, 1990. 8. I{oo, L.C., et al. "An Analysis of Some Risk Factors for Lung Cancer in Hong Kong," Int. J. Cancer 35: 139-155, 1985. 9. Mantel, N., "Chi-Square Tests with One Degree of Freedom: Extension of the Mantel-Haenszel Procedure," J. Am, t~ a. Assoc. 59: 670-700. 10. Henderson, B.E., et al. "Smoking and Other Risk Fators for Lung Cancer in Women," JNCx 74(4): 747-751. - 8 -