Association of CYP1A1, CYP1A2, GSTM1 and NAT2 Gene Polymorphisms with Colorectal Cancer Risk and Smoking


We investigated CYP1A1*2A, CYP1A1*2C, CYP1A2*1C, CYP1A2*1F, GSTM1 and NAT2 genepolymorphisms, involving enzymes which metabolize many carcinogens, with reference to colorectal cancerrisk. The distribution of these genotypes was not associated with risk overall. However, the CYP1A1*2A T/Cgenotype showed a significant association with colorectal cancer risk in never-smokers (odds ratio [OR], 3.06;95% confidence interval [95% CI], 1.11-8.40; p = 0.030). The risk of the NAT2 rapid genotype in never-smokerswas also statistically significantly increased (OR, 5.38; 95%CI, 1.80-16.1; p = 0.003). Furthermore, the jointeffects of NAT2 rapid plus other genotypes were associated with colorectal cancer overall (OR, 3.12; 95%CI,1.15-8.51; p = 0.026, for NAT2 rapid plus combined CYP1A1*2C Ile/Val and Val/Val, OR, 3.25; 95%CI, 1.09-9.74; p = 0.035, for NAT2 rapid plus CYP1A2*1C G/G, and OR, 4.20; 95%CI, 1.09-16.1; p = 0.037, for NAT2rapid plus GSTM1 null, respectively). In never-smokers, the joint effects of NAT2 rapid plus other genotypeswere remarkable (OR, 15.9; 95%CI, 1.87-135.8; p = 0.011, for NAT2 rapid plus combined CYP1A1*2A T/Cand C/C, OR, 5.71; 95%CI, 1.49-21.9; p = 0.011, for NAT2 rapid plus combined CYP1A1*2C Ile/Val and Val/Val, and OR, 9.14; 95%CI, 2.05-40.7; p = 0.004, for NAT2 rapid plus CYP1A2*1F A/A, respectively). The jointeffect of CYP1A2*1F A/A plus CYP1A2*1C G/G genotypes was also increased in never-smokers (OR, 6.16;95%CI, 1.26-30.1; p = 0.025). Our findings suggest that the CYP1A1*2A T/C and NAT2 rapid genotypes isassociated with colorectal cancer susceptibility without smoking exposure. These results also indicate that theNAT2 in combination with CYP1A1*2C, CYP1A2*1C, or GSTM1 genotypes may strongly confer susceptibilityto colorectal cancer. In particular, the combination of NAT2 plus CYP1A1*2A, CYP1A1*2C, or CYP1A2*1Fgenotypes, and that of CYP1A2*1F plus CYP1A2*1C genotype may define a group of persons who are geneticallysusceptible to colorectal cancer in never smokers.