Carcinogenesis Advance Access originally published online on August 21, 2006
Carcinogenesis 2007 28(2):328-341; doi:10.1093/carcin/bgl135
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Inherited variation in carcinogen-metabolizing enzymes and risk of colorectal polyps
1 Cancer Prevention Program, Fred Hutchinson Cancer Research Center Seattle, WA, USA
2 Department of Epidemiology, University of Washington Seattle, WA, USA
3 Department of Health Sciences Research, Mayo Clinic College of Medicine Rochester, MN, USA
*To whom correspondence should be addressed at: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Tel: +1 507 266 7997; Fax: +1 507 266 2478; Email: egoode{at}mayo.edu
Exposures such as cigarette smoke and meat contain a variety of procarcinogens, which are thought to play a role in elevation of risk for colorectal polyps and/or cancer. These procarcinogens (including heterocyclic amines and polycyclic aromatic hydrocarbons) are metabolized by a variety of polymorphic enzymes including N-acetyltransferases, sulfotransferases, cytochrome P450 enzymes and epoxide hydrolase. We hypothesized that genetic variation in the encoding genes NAT1, NAT2, SULT1A1, SULT1A2, CYP1A1 or EPHX1 is associated with risk of colorectal polyps and interacts with cigarette use or meat intake to modify risk of colorectal polyps. We examined the role of these genes in a clinic-based study of 651 Caucasian cases with hyperplastic polyps, adenomatous polyps or both types of polyps and 556 polyp-free controls. We found evidence for interaction between NAT acetylator status and SULT1A1 genotype in risk of hyperplastic polyps: individuals with SULT1A1 638AA genotype and NAT1 and NAT2 intermediate/fast phenotypes had 3.5-fold increased risk (95% CI 1.2–10.3) compared with individuals with SULT1A1 638GG genotype and NAT1 and NAT2 slow phenotypes. Data were also consistent with interactions between smoking and variation in SULT1A1, CYP1A1 and EPHX1 and between meat intake and variation in CYP1A1 and EPHX1. No interactions were statistically significant. Although results should be interpreted with caution considering sample size and the number of hypotheses examined, our study suggests future avenues of investigation in larger investigations of genetic and lifestyle factors in the pathway to colorectal cancer.
Abbreviations: AAs, aromatic amines; CYPs, cytochrome P450 enzymes; FAP, familial adenomatous polyposis; HAs, heterocyclic amines; LD, linkage disequilibrium; MAFs, minor allele frequencies; NSAIDs, non-steroidal anti-inflammatory drugs; PAHs, polycyclic aromatic hydrocarbons; SNPs, single nucleotide polymorphisms; SULTs, sulfotransferases
Received March 31, 2006; revised June 27, 2006; accepted June 30, 2006.
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