Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer

Polymorphisms in glutathione S-transferases (GSTs) may predispose to colore ctal cancer through deficient detoxtification of environmental carcinogens, although previous results are conflicting. A study with 178 matched case-c ontrol pairs was conducted to determine the effect of the GSTT1 and GSTM1;l l null genotypes and polymorphisms in GSTP1 on colorectal cancer susceptibi lity. In a secondary analysis, we examined interactions between genotypes a nd with the N-acetyltransferase 2 (NAT2) genotype, Heterogeneity by age, se x, site, and stage of cancer was also examined. No effect of any genotype f or GSTM1, GSTT1, or GSTP1 on colorectal cancer susceptibility was detected. Secondary end points showed that individuals with both the GSTT1 null and NAT2 slow genotypes combined appeared to be at increased risk of colorectal cancer (odds ratio = 233; 95% confidence interval 1.1-5.0), We conclude th at GST polymorphisms alone do not predispose to colorectal cancer in northe ast England. We also observed possible effects of the GSTT1 null genotype o n the age and stage at presentation, and these, together with the findings of an apparent interaction with NAT2 genotypes, need to be confirmed in fur ther studies.