Glutathione S-transferase (GST) M1 and T1 genes encode GST enzymes, and are polymorphic in humans. These enzymes catalyze conjugation with glutathione, which is an important step in the detoxification of certain carcinogens. Several case-control studies have found associations of the homozygous null deletions in GSTM1 and GSTT1 with increasing the risk of colorectal and lung cancer. We prospectively examined the associations of the GSTM1 and GSTT1 polymorphisms with colorectal cancer risk in a nested case-control study (212 cases of colorectal cancer and 221 controls) within the Physicians' Health Study. Among controls, the prevalence of the GSTM1 homozygous null genotype was 53% and for GSTT1 homozygous null genotype, 23%. We found no increase in the risk of colorectal cancer for either GSTM1 null [odds ratio (OR) = 1.0; 95% confidence interval (CI), 0.7-1.5] or GSTT1 null (OR = 0.8; 95% CI, 0.5-1.2) genotypes. No differences were seen by site of colon cancer (proximal versus distal) or by age (< or = 60 years versus > 60 years). Current cigarette smokers with GSTM1 null genotype were not at an increased risk of colon cancer (OR = 1.2; 95% CI, 0.3-4.2) compared with current smokers without the null genotype; for the GSTT1 null genotype this OR was 1.1 = 95% CI (0.3-4.7). This lack of association persisted when we examined pack-years of smoking and age at starting smoking. Our results do not support an association of GSTM1 or GSTT1 polymorphisms with colorectal cancer or an interaction with cigarette smoking.

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