Glutathione Transferase (GSTM1) Null Genotype, Smoking, and Prevalence of Colorectal Adenomas1

Colorectal cancer is caused by environmental exposures and genetic predisposition. However, little is known of hereditary factors that influ ence development of common, non-Mendelian forms of this cancer. Inter actions among carcinogen exposure, hereditary variants of enzymes in volved in carcinogen metabolism, and other host factors may play a role. Genetic polymorphisms of carcinogen metabolism, such as the glutathione transferase Ml (GSTM1) null genotype, are thus possibly related to cancer risk. The GSTM1 enzyme detoxifies mutagens formed from polycyclic aromatic hydrocarbons which are found in tobacco smoke. We analyzed GSTM1 genotypes and smoking among 488 controls and 446 individuals with a first time diagnosis of colorectal adenomas which are precursors to cancer. Subjects were from two Kaiser Permanente sigmoidoscopy clinics in southern California. We observed no overall effect of the GSTM1 null genotype on the risk for colorectal adenomas (odds ratio, 0.85; 95% confidence interval = 0.65-1.10). The odds ratio for smokers with the null genotype was 2.07 (95% confidence interval = 1.14-3.77) when compared to "never smokers" without the null genotype. Using this same reference group, the odds ratio for smokers without the null geno type was 1.73 (95% confidence interval = 1.03-2.90). These two odds ratios were not significantly different (/' = 0.30).