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Carcinogenesis Advance Access published online on February 24, 2005
Carcinogenesis, doi:10.1093/carcin/bgi054
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Published by Oxford University Press 2005
Received September 21, 2004
Revised February 15, 2005
Accepted February 16, 2005

CARCINOGENESIS

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

Lifang Hou 1*, Nilanjan Chatterjee 1, Wen-Yi Huang 1, Andrea Baccarelli 1, Sunita Yadavalli 2, Meredith Yeager 2, Robert S. Bresalier 3, Stephen J. Chanock 4, Neil E. Caporaso 1, Bu-Tian Ji 1, Joel L. Weissfeld 5, and Richard B. Hayes 1

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Human and Health Services, Bethesda, MD
2 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Human and Health Services, Bethesda, MD; SAIC-Frederick, National Cancer Institute, Frederick, MD
3 Department of Gastrointestinal Medicine and Nutrition, MD Anderson Cancer Center, Houston, TX
4 Section of Genomic Variation, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda MD
5 Department of Epidemiology, University of Pittsburgh Cancer Institute, Pittsburgh, PA

* To whom correspondence should be addressed.
Lifang Hou, E-mail: lifangh2{at}mail.nih.gov


  Abstract

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 (PLCO) Screening Trial. CYP1A1 Val462 and NQO1 Ser187 individually 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 to 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.

Keywords: Polymorphisms; Smoking; Colorectal Adenoma; PLCO Trial.
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