Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism

Glutathione S-transferase (GST) polymorphism may contribute to the individu al variability in detoxifying lung carcinogens. This effect might be partic ularly 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 nonsmoki ng controls from eight countries. Information on environmental exposures wa s obtained through a personal interview. The presence of GSTM1 and GSTT1 ge nes was determined using multiplex PCR, GSTM1-positive samples were then an alyzed for *1A and *1B polymorphism using an allele-specific amplification- PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cance r 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 carcinogen s (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed to ETS, GSTT1*2 s ubjects did not show a risk of lung cancer. Our study suggests that the eff ect of GSTMI polymorphism in nonsmokers is similar to that found in smokers . It does not seem to interact with ETS exposure, although we cannot exclud e that it does in association with exposure to other specific environmental carcinogens.