NAT2, GSTM-1, cigarette smoking, and risk of colon cancer

Cigarette smoking has been associated inconsistently with colon cancer, The extent to which genetic profile influences susceptibility to the inducemen t of colon cancer by cigarette smoking is not known. In this study, we eval uated the associations between smoking cigarettes and polymorphisms of the NAT2 and GSTM-1 genes using data obtained from an incident case-control stu dy of 1993 cases of colon cancer and 2410 age- and sex- matched controls, N either NAT2 nor GSTM-1 polymorphisms were significantly associated with col on cancer, except among older women, in whom the intermediate/rapid imputed phenotype was associated with increased risk of colon cancer [odds ratio ( OR) = 1.4, 95% confidence interval (CI) = 1.0-1.8], Using several indicator s of cigarette smoking, we observed no significant interaction between thes e genotypes and cigarette smoking and colon cancer, The major variation in association,vith colon cancer was from the amount of cigarette exposure, wi th those smoking a pack or more of cigarettes per day being at an similar t o 40% increased risk of colon cancer; this association did not vary by geno type, However, those who stopped smoking 5-14 years prior to diagnosis and who where intermediate/rapid acetylators were at a slightly greater risk th an those who were slow acetylators (for men, OR = 1.6, 95% CI = 1.0-2.4; fo r women, OR = 2.5, 95% CI = 1.4-4.4), Associations were similar when proxim al and distal tumors were examined and separated for age at the time of dia gnosis. The lack of an association does not rule out the possibility of oth er genetic polymorphisms interacting with cigarette smoke to cause colon ca ncer, nor does it take into account individual phenotypic variability.