| Abstrakt: |
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 = 1.14.5), particularly among recent (including current) (OR = 17.4, 95% CI = 3.879.8, P for interaction = 0.02) and heavy cigarette smokers (>20 cigarettes/day) (OR = 21.1, 95% CI = 3.9114.4, 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. [ABSTRACT FROM AUTHOR] |
