Effect of vitamin intervention on the relationship between GSTM1, smoking,and lung cancer risk among male smokers

The GSTM1 (glutathione S-transferase mu-l) null genotype is suspected of in creasing an individual's susceptibility to tobacco smoke carcinogens becaus e of impaired carcinogen detoxification, We were interested in whether ther e were differences in lung cancer susceptibility to smoking within the GSTM 1 genotypes and the impact of antioxidant supplementation on this. For this purpose, we conducted a nested lung cancer case-control study and evaluate d the role of GSTM1 within the Alpha-Tocopherol, Beta-Carotene Cancer Preve ntion Study. GSTM1 genotype status was determined for 319 cases and 333 con trols using a PCR-based approach, GSTM1 was evaluated as an independent ris k factor and as an effect modifier of smoking using logistic regression ana lyses. The GSTM1 null genotype itself was unrelated to risk of lung cancer, odds ratio (OR) = 1.09 and 95% confidence interval (CI), 0.79-1.50, but it may have modified the effect of smoking. There was a suggestion for a stro nger association between years of smoking and lung cancer among the GSTM1 n ull genotype, but the differences between GSTM1 null and present genotypes were not statistically significant (P = 0.12), Furthermore, the smoking ass ociation was strongest among those with the GSTM1 null genotype not receivi ng a-tocopherol supplementation, whereas among those receiving alpha-tocoph erol, there was no modification by GSTM1 on the association between smoking duration and lung cancer risk. beta-Carotene supplementation did not modif y the relationship between GSTM1, smoking years, and lung cancer risk. In c onclusion, GSTM1 is not associated with lung cancer risk in male smokers bu t may confer a higher susceptibility to cumulative tobacco exposure. This a ssociation may be attenuated by alpha-tocopherol but not by beta-carotene s upplementation.