© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 9, 760,
May 3, 2000
© 2000 Oxford University Press
CORRESPONDENCE |
Re: Environmental Tobacco Smoke, Genetic Susceptibility, and Risk of Lung Cancer in Never-Smoking Women
Correspondence to: Anthony R. Tricker, Ph.D., Philip Morris Europe, Worldwide Scientific Affairs, CH 2003 Neuchâtel, Switzerland.
Bennett et al. (1) report that never-smoking Missouri women who report exposure to environmental tobacco smoke (ETS) and develop lung cancer are more likely to be deficient in GSTM1 activity (GSTM1 null genotype) compared with never smokers who had no ETS exposure and developed lung cancer (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.1–6.1). It is further concluded that "For the half of the population of never-smoking women with the GSTM1 null polymorphism, ETS exposure is responsible for between 42% and 49% of the lung cancer cases."
Yet in an accompanying editorial, Weinberg and Sandler (2) comment: "Clearly, many questions remain, and the reported interaction (1) between GSTM1 and ETS requires confirmation." They also point out that an OR of 2.6 for the association of ETS exposure with lung cancer in GSTM1 null nonsmoking women suggests a relative risk of at least 1.7 for the association of ETS with lung cancer in nonsmoking women, which is inconsistent with generally accepted estimates (3), including the reported OR of 1.1 (95% CI = 0.8–1.3) for Missouri women (4).
The International Agency for Research on Cancer has investigated genetic polymorphisms of GSTM1 and GSTT1 in nonsmokers and their interaction with exposure to ETS in a multicenter case–control study of 115 nonsmoking lung cancer case subjects, in 177 smoking lung cancer case subjects, and in 109 nonsmoking hospital or population control subjects (5). The GSTM1 null genotype was not associated with risk of lung cancer in nonsmokers (OR = 0.97; 95% CI = 0.55–1.72) and with a modest, not statistically significant, increase in risk in smokers (OR = 1.70; 95% CI = 0.71–4.05). GSTT1 null genotypes were associated with decreased risk in both nonsmokers (OR = 0.65; 95% CI = 0.35–1.19) and smokers (OR = 0.92; 95% CI = 0.34–2.48). Nonsmoking case subjects experienced higher levels of ETS exposure than control subjects. It was concluded that "These results do not suggest a role of GST M1 or T1 polymorphisms as modifying factors of lung cancer risk due to ETS exposure in nonsmokers."
Further, Nyberg et al. (6), in a study of 185 male and female nonsmoking and smoking lung cancer patients and 164 frequency-matched population control subjects, reported an overall OR for lung cancer associated with the GSTM1 null genotype of 0.8 (95% CI = 0.5–1.2), with an OR close to unity among ever smokers (OR = 0.9; 95% CI = 0.4–1.9) and lower among never smokers (OR = 0.6; 95% CI = 0.3–1.1). The risk of lung cancer was almost identical among never smokers reporting exposure to ETS from the spouse or at work during the last 10 years before diagnosis (OR = 0.7; 95% CI = 0.2–1.9) and those reporting no exposure to ETS (OR = 0.6; 95% CI = 0.2–1.0).
Clearly, epidemiologic approaches that use either case-only (1) or case–control (5,6) designs differ, making it hard to conclude whether individuals with germline polymorphisms in genes for enzymes that detoxify environmental genotoxins are at increased risk of lung cancer due to exposure to ETS.
NOTES
Editor's note: A. R. Tricker is employed by the tobacco industry.
REFERENCES
1
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.
2
Weinberg CR, Sandler DP. Gene-by-environment interaction for passive smoking and glutathione S-transferase M1? [editorial]. J Natl Cancer Inst 1999;91:1985–6.
3
Hackshaw AK, Law MR, Wald NJ. The accumulated evidence on lung cancer and environmental tobacco smoke. BMJ 1997;315:980–8.
4
Brownson RC, Alavanja MC, Hock ET, Loy TS. Passive smoking and lung cancer in nonsmoking women. Am J Public Health 1992;82:1525–30.
5 Malats N, Camus-Randon AM, Nyberg F, Ahrens W, Constantinescu V, Mukeria A, et al. Does GST M1 and T1 gene polymorphism modify environmental tobacco smoke effect on lung cancer? [abstract] Proc Am Assoc Cancer Res 1998;39:182.
6 Nyberg F, Hou SM, Hemminki K, Lambert B, Pershagen G. Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls. Cancer Epidemiol Biomarkers Prev 1998;7:875–83.[Abstract]cancerlit;99010656
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