Glutathione S-Transferase GSTM1 AND GSTI’l Polymorphisms and Colorectal Cancer Risk: A Prospective

Glutathione S-transferase (GST) Ml and Ti 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 GSTMJ and GS1TJ with increasing the risk of colorectal and lung cancer. We prospectively examined the associations of the GSTMJ and GSTTJ 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 GSTMJ homozygous null genotype was 53% and for GSTTJ homozygous null genotype, 23%. We found no increase in the risk of colorectal cancer for either GSTMJ null [odds ratio (OR) = 1.0; 95% confidence interval (CI), 0.7-1.51 or GSTTJ 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 ( 60 years versus >60 years). Current cigarette smokers with GSTMJ 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 GSTTI 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 GSTMJ or GSTTJ polymorphisms with colorectal cancer or an interaction with cigarette smoking.