title: Interaction of cigarette smoking and carcinogen-metabolizing polymorphisms in the risk of colorectal polyps.
abstract: The causal role of cigarette smoking in the risk of colorectal neoplasm has been suggested but not established. In a case-control study including 2060 colorectal polyp patients and 3336 polyp-free controls, we evaluated 21 functional genetic variants to construct a tobacco-carcinogen-metabolizing genetic risk score. Data regarding cigarette smoking were obtained through telephone interviews. Cigarette smoking was associated with an elevated risk of both adenomas and hyperplastic polyps. The association with smoking was stronger in participants with a high carcinogen-metabolizing risk score than those with a low risk score. Smoking 30 or more cigarettes per day was associated with a 1.7-fold elevated risk of any polyps (95% confidence interval = 1.3-2.2) among those with a low genetic risk score and 2.9-fold elevated risk (95% confidence interval = 1.8-4.8) among those with a high genetic risk score (P interaction = 0.025). A similar pattern of interaction was observed in analyses conducted separately for those with adenomas only (P interaction = 0.039) and hyperplastic polyps only (P interaction = 0.024). Interaction between carcinogen-metabolizing genetic risk and cigarette smoking was found in relation to high-risk adenomas (P interaction = 0.010) but not low-risk adenomas (P interaction = 0.791). No apparent interaction was found for duration of smoking. This study shows that the association between cigarette smoking and colorectal polyp risk is modified by tobacco-carcinogen-metabolizing polymorphisms, providing support for a causal role of cigarette smoking in the etiology of colorectal tumors.
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Fu
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Shrubsole
authors.forename: Guoliang
authors.initials: G
authors.lastname: Li
authors.forename: Walter E
authors.initials: WE
authors.lastname: Smalley
authors.forename: David W
authors.initials: DW
authors.lastname: Hein
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Reid M
authors.initials: RM
authors.lastname: Ness
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000236:Adenoma / Q000209:etiology / Q000235:genetics; D000328:Adult; D000368:Aged; D002273:Carcinogens / Q000378:metabolism*; D016022:Case-Control Studies; D003111:Colonic Polyps / Q000209:etiology / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics*; D004198:Disease Susceptibility; D004798:Enzymes / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006965:Hyperplasia / Q000150:complications; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution; D014026:Nicotiana
chemical_list: D002273:Carcinogens; D004798:Enzymes; D014028:Tobacco Smoke Pollution