Environmental tobacco smoke and risk of respiratory cancer and chronic
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《英国医生杂志》
1 Imperial College, London W2 1PG
Correspondence to: P Vineis p.vineis@imperial.ac.uk
Abstract
Environmental tobacco smoke, or involuntary smoking, comprises sidestream smoke from the smouldering tobacco between puffs and exhaled mainstream smoke from the smoker. More than 50 investigations, mostly case-control studies, have shown that involuntary smoking is associated with an increased risk for lung cancer.1 2 In 2002, a working group of the International Agency for Research on Cancer evaluated the epidemiological evidence and included environmental tobacco smoke in group I (human carcinogen).3 4 Few cohort studies are available, however, with accurate information on potential confounders or effect modifiers. We analysed data from the large European prospective investigation into cancer and nutrition (EPIC) to assess the relation between environmental tobacco smoke and lung cancer, upper respiratory cancers, and death from chronic obstructive pulmonary disease (COPD) or emphysema, limiting our analysis to never smokers and people who had not smoked for more than 10 years. The advantage of the cohort design is the lack of recall bias as information about exposure was collected before onset of disease.
Methods
Information on exposure to environmental tobacco smoke was collected from 123 479/303 020 (40.8%) participants who had never smoked or former smokers in the EPIC cohort. Of these 97 people developed lung cancer, 20 developed upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema during the seven years of follow up. Table 1 shows details for cases, controls, and the whole cohort.
Table 1 Distribution of cases and controls by relevant variables
Plasma cotinine was measured in 1574 GenAir subjects (with or without information on environmental tobacco smoke). The method was highly specific and sensitive with a detection limit of 0.05 ng of cotinine per ml of plasma in 50 μl samples. We excluded 47 participants with values > 10 ng/ml because they were likely to be active smokers (n = 41) or sniffers/chewers (n = 6). Of the 1527 remaining subjects, 461 (30%) had detectable concentrations of plasma cotinine with an overall mean value of 0.92 ng/ml (SD 0.96 ng/ml). Table 2 shows the mean cotinine concentrations in the 374 people with information on environmental tobacco smoke. Cotinine concentrations were clearly associated with self reported exposure to environmental tobacco smoke (odds ratio 3.30, 95% confidence interval 2.07 to 5.23, for detectable/non-detectable cotinine, P < 0.0001). We did not reassess environmental tobacco smoke after cotinine measurements—that is, these are two independent sources of information.
Table 2 Cotinine measurements in 374 people* with information on exposure to environmental tobacco smoke
Table 3 shows results for the whole cohort (Cox's proportional hazards model) and for the nested case-control study (conditional regression models). Increased odds ratios and hazard ratios were associated with environmental tobacco smoke exposure at recruitment for all respiratory diseases and for lung cancer alone in the whole cohort and in the nested study. Higher odds ratios were observed separately in each country (data not shown; test for heterogeneity, P = 0.08). The differences observed in risks associated with environmental tobacco smoke between sexes were not significant (test for heterogenity P = 0.66).
Table 3 Environmental tobacco smoke (ETS) exposure (home and/or work) and respiratory disease (including deaths from lung cancer, larynx or pharynx cancer, and deaths from chronic obstructive pulmonary disease) or lung cancer alone, in whole cohort (n=123 479, 131 cases) and in nested case-control study (n=114 cases, 286 controls)
Former smokers had higher risks for respiratory disease (attaining significance) than those who had never smoked in both the whole cohort and the case-control analyses. The raised risks in both analyses, were limited to exposures related to work, with significant risk estimates around 1.5 to 2.0. Cotinine was not associated with lung cancer or other diseases. The odds ratio for detectable versus undetectable cotinine concentrations and respiratory disease/cancer was 0.9 (0.5 to 1.8).
Table 4 shows the distribution of self reported exposure to environmental tobacco smoke during childhood in those who had never smoked, in the centres where information was collected (n = 60 182). Increased risks were present for the categories "daily" and "daily, many hours," with significant confidence intervals for the latter.
Table 4 Cox's proportional hazards model for relation between exposure to environmental tobacco smoke in childhood and risk of lung cancer in whole cohort in 60 182 people who have never smoked
We analysed the role of environmental tobacco smoke in lung cancer according to the score of "at risk" alleles for polymorphisms in metabolic genes. The odds ratio associated among carriers of at least three of the at risk polymorphisms was 2.86 (0.79 to 10.35), while for those with one or two alleles it was 1.33 (0.82 to 2.18). This difference was detected in unconditional analysis because numbers were too small for conditional analysis.
Discussion
Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke. BMJ 1997;315: 980-8.
Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 2004;96: 99-106.
International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans. Vol 83. Lyons: International Agency for Research on Cancer (in press).
Benowitz NL. Biomarkers of environmental tobacco smoke exposure. Environ Health Perspect 1999;107(suppl 2): 349-55.
Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M, et al. European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 2002;5(6B): 1113-24.
Vineis P, Malats N, Lang M, d'Errico A, Caporaso N, Cuzick J, Boffetta P. Metabolic polymorphisms and susceptibility to cancer. Lyons: International Agency for Research on Cancer, 1999. (IARC Sci Publ No 148.)
Korn EL, Graubard BI, Midthune D. Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale. Am J Epidemiol 1997;145: 72-80.
Breslow NE, Day NE. Statistical methods in cancer research. Vol I. The analysis of case-control studies. Lyons: International Agency for Research on Cancer, 1980. (IARC Sci Publ No 32.)
Davey Smith G, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol 2004;33: 30-42.
Kiyohara C, Wakai K, Mikami H, Sido K, Ando M, Ohno Y. Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of environmental tobacco smoke and lung cancer: a case-control study in Japanese nonsmoking women. Int J Cancer 2003;107: 139-44.
Bennett WP, Alavanja MC, Blomeke B, Vahakangas KH, Castren K, Welsh JA, et al. Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. J Natl Cancer Inst 1999;91: 2009-14.
Malats N, Camus-Radon AM, Nyberg F, Ahrens W, Constantinescu V, Mukeria A, et al. Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphisms. Cancer Epidemiol Biomarkers Prev 2000;9: 827-33.
Lee CH, Ko YC, Goggins W, Huang JJ, Huang MS, Kao EL, Wang HZ. Lifetime environmental exposure to tobacco smoke and primary lung cancer of non-smoking Taiwanese women. Int J Epidemiol 2000;29: 224-31.
Tredaniel J, Boffetta P, Little J, Saracci R, Hirsch A. Exposure to passive smoking during pregnancy and childhood, and cancer risk: the epidemiological evidence. Paediatr Perinat Epidemiol 1994;8: 233-55.
Hecht SS, Ye M, Carmella SG, Fredrickson A, Adgate JL, Greaves IA, et al. Metabolites of a tobacco-specific lung carcinogen in the urine of elementary school-aged children. Cancer Epidemiol Biomarkers Prev 2001;10: 1109-16.(P Vineis, epidemiologist1, L Airoldi, F )
Correspondence to: P Vineis p.vineis@imperial.ac.uk
Abstract
Environmental tobacco smoke, or involuntary smoking, comprises sidestream smoke from the smouldering tobacco between puffs and exhaled mainstream smoke from the smoker. More than 50 investigations, mostly case-control studies, have shown that involuntary smoking is associated with an increased risk for lung cancer.1 2 In 2002, a working group of the International Agency for Research on Cancer evaluated the epidemiological evidence and included environmental tobacco smoke in group I (human carcinogen).3 4 Few cohort studies are available, however, with accurate information on potential confounders or effect modifiers. We analysed data from the large European prospective investigation into cancer and nutrition (EPIC) to assess the relation between environmental tobacco smoke and lung cancer, upper respiratory cancers, and death from chronic obstructive pulmonary disease (COPD) or emphysema, limiting our analysis to never smokers and people who had not smoked for more than 10 years. The advantage of the cohort design is the lack of recall bias as information about exposure was collected before onset of disease.
Methods
Information on exposure to environmental tobacco smoke was collected from 123 479/303 020 (40.8%) participants who had never smoked or former smokers in the EPIC cohort. Of these 97 people developed lung cancer, 20 developed upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema during the seven years of follow up. Table 1 shows details for cases, controls, and the whole cohort.
Table 1 Distribution of cases and controls by relevant variables
Plasma cotinine was measured in 1574 GenAir subjects (with or without information on environmental tobacco smoke). The method was highly specific and sensitive with a detection limit of 0.05 ng of cotinine per ml of plasma in 50 μl samples. We excluded 47 participants with values > 10 ng/ml because they were likely to be active smokers (n = 41) or sniffers/chewers (n = 6). Of the 1527 remaining subjects, 461 (30%) had detectable concentrations of plasma cotinine with an overall mean value of 0.92 ng/ml (SD 0.96 ng/ml). Table 2 shows the mean cotinine concentrations in the 374 people with information on environmental tobacco smoke. Cotinine concentrations were clearly associated with self reported exposure to environmental tobacco smoke (odds ratio 3.30, 95% confidence interval 2.07 to 5.23, for detectable/non-detectable cotinine, P < 0.0001). We did not reassess environmental tobacco smoke after cotinine measurements—that is, these are two independent sources of information.
Table 2 Cotinine measurements in 374 people* with information on exposure to environmental tobacco smoke
Table 3 shows results for the whole cohort (Cox's proportional hazards model) and for the nested case-control study (conditional regression models). Increased odds ratios and hazard ratios were associated with environmental tobacco smoke exposure at recruitment for all respiratory diseases and for lung cancer alone in the whole cohort and in the nested study. Higher odds ratios were observed separately in each country (data not shown; test for heterogeneity, P = 0.08). The differences observed in risks associated with environmental tobacco smoke between sexes were not significant (test for heterogenity P = 0.66).
Table 3 Environmental tobacco smoke (ETS) exposure (home and/or work) and respiratory disease (including deaths from lung cancer, larynx or pharynx cancer, and deaths from chronic obstructive pulmonary disease) or lung cancer alone, in whole cohort (n=123 479, 131 cases) and in nested case-control study (n=114 cases, 286 controls)
Former smokers had higher risks for respiratory disease (attaining significance) than those who had never smoked in both the whole cohort and the case-control analyses. The raised risks in both analyses, were limited to exposures related to work, with significant risk estimates around 1.5 to 2.0. Cotinine was not associated with lung cancer or other diseases. The odds ratio for detectable versus undetectable cotinine concentrations and respiratory disease/cancer was 0.9 (0.5 to 1.8).
Table 4 shows the distribution of self reported exposure to environmental tobacco smoke during childhood in those who had never smoked, in the centres where information was collected (n = 60 182). Increased risks were present for the categories "daily" and "daily, many hours," with significant confidence intervals for the latter.
Table 4 Cox's proportional hazards model for relation between exposure to environmental tobacco smoke in childhood and risk of lung cancer in whole cohort in 60 182 people who have never smoked
We analysed the role of environmental tobacco smoke in lung cancer according to the score of "at risk" alleles for polymorphisms in metabolic genes. The odds ratio associated among carriers of at least three of the at risk polymorphisms was 2.86 (0.79 to 10.35), while for those with one or two alleles it was 1.33 (0.82 to 2.18). This difference was detected in unconditional analysis because numbers were too small for conditional analysis.
Discussion
Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke. BMJ 1997;315: 980-8.
Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, et al. Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 2004;96: 99-106.
International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans. Vol 83. Lyons: International Agency for Research on Cancer (in press).
Benowitz NL. Biomarkers of environmental tobacco smoke exposure. Environ Health Perspect 1999;107(suppl 2): 349-55.
Riboli E, Hunt KJ, Slimani N, Ferrari P, Norat T, Fahey M, et al. European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 2002;5(6B): 1113-24.
Vineis P, Malats N, Lang M, d'Errico A, Caporaso N, Cuzick J, Boffetta P. Metabolic polymorphisms and susceptibility to cancer. Lyons: International Agency for Research on Cancer, 1999. (IARC Sci Publ No 148.)
Korn EL, Graubard BI, Midthune D. Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale. Am J Epidemiol 1997;145: 72-80.
Breslow NE, Day NE. Statistical methods in cancer research. Vol I. The analysis of case-control studies. Lyons: International Agency for Research on Cancer, 1980. (IARC Sci Publ No 32.)
Davey Smith G, Ebrahim S. Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol 2004;33: 30-42.
Kiyohara C, Wakai K, Mikami H, Sido K, Ando M, Ohno Y. Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of environmental tobacco smoke and lung cancer: a case-control study in Japanese nonsmoking women. Int J Cancer 2003;107: 139-44.
Bennett WP, Alavanja MC, Blomeke B, Vahakangas KH, Castren K, Welsh JA, et al. Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. J Natl Cancer Inst 1999;91: 2009-14.
Malats N, Camus-Radon AM, Nyberg F, Ahrens W, Constantinescu V, Mukeria A, et al. Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphisms. Cancer Epidemiol Biomarkers Prev 2000;9: 827-33.
Lee CH, Ko YC, Goggins W, Huang JJ, Huang MS, Kao EL, Wang HZ. Lifetime environmental exposure to tobacco smoke and primary lung cancer of non-smoking Taiwanese women. Int J Epidemiol 2000;29: 224-31.
Tredaniel J, Boffetta P, Little J, Saracci R, Hirsch A. Exposure to passive smoking during pregnancy and childhood, and cancer risk: the epidemiological evidence. Paediatr Perinat Epidemiol 1994;8: 233-55.
Hecht SS, Ye M, Carmella SG, Fredrickson A, Adgate JL, Greaves IA, et al. Metabolites of a tobacco-specific lung carcinogen in the urine of elementary school-aged children. Cancer Epidemiol Biomarkers Prev 2001;10: 1109-16.(P Vineis, epidemiologist1, L Airoldi, F )