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Lung Cancer Risk in Nonsmokers and GSTM1 and GSTT1 Genetic Polymorphism¹

International Agency for Research on Cancer, F-69372 Lyon, France [N. M., A-M. C-R., S. L., M. L., P. B.]; Institut Municipal d’Investigació Mèdica, E-08003 Barcelona, Spain [N. M.]; Institute of Environmental Medicine, Karolinska Institute, S-17177 Stockholm, Sweden [F. N.]; Bremen Institute for Prevention Research, D-28199 Bremen, Germany [W.A.]; Institute of Public Health, R-76256 Bucharest, Romania [V. C.]; Institute of Carcinogenesis, Cancer Research Center, 115478 Moscow, Russia [A. Mu.]; INSERM U157, F-94805 Villejuif, France [S. B.]; Pneumological Hospital, 60-568 Poznan, Poland [H. B-G.]; GSF Institute for Epidemiology, D-85758 Munich, Germany [I. B-H.]; Veneto Cancer Registry, Department of Oncology, University of Padua, I-35128 Padua, Italy [L. S.]; Federal University of Rio Grande do Sul, 96100 Pelotas, RG, Brazil [A. Me.]; School of Public Health, University of California, Berkeley, California 94720-7360 [S. L.]; and Uppsala University, S-75123 Uppsala, Sweden [M. L.]

Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9–2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9–6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9–9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0–13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4–260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.

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