CYP1A1 Val₄₆₂ and NQO1 Ser₁₈₇ polymorphisms, cigarette use, and risk for colorectal adenoma

Cigarette use is a risk factor for colorectal adenoma, a known precursor of colorectal cancer. Polymorphic variants in NQO1 and CYP1A1 influence the activation of carcinogenic substances in tobacco smoke, possibly impacting on tobacco-associated risks for colorectal tumors. We investigated the association of cigarette smoking with risk for advanced colorectal adenoma in relation to the CYP1A1 Val₄₆₂ and NQO1 Ser₁₈₇ polymorphic variants. Subjects were 725 non-Hispanic Caucasian cases with advanced colorectal adenoma of the distal colon (descending colon, sigmoid and rectum) and 729 gender- and ethnicity-matched controls, randomly selected from participants in the prostate, lung, colorectal and ovarian cancer screening trial. Subjects carrying either CYP1A1 Val₄₆₂ or NQO1 Ser₁₈₇ alleles were weakly associated with risk of colorectal adenoma; however, subjects carrying both CYP1A1 Val₄₆₂ and NQO1 Ser₁₈₇ alleles showed increased risks (OR = 2.2, 95% CI = 1.1-4.5), particularly among recent (including current) (OR = 17.4, 95% CI = 3.8-79.8, P for interaction = 0.02) and heavy cigarette smokers (>20 cigarettes/day) (OR = 21.1, 95% CI = 3.9-114.4, P for interaction = 0.03) compared with non-smokers who did not carry either of these variants. These genotypes were unassociated with risk in non-smokers. In analysis of adenoma subtypes, the combined gene variants were most strongly associated with the presence of multiple adenoma (P = 0.002). In summary, joint carriage of CYP1A1 Val₄₆₂ and NQO1 Ser₁₈₇ alleles, particularly in smokers, was related to colorectal adenoma risk, with a propensity for formation of multiple lesions.