Carcinogenesis Advance Access published online on August 21, 2006
Carcinogenesis, doi:10.1093/carcin/bgl135
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1 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
* To whom correspondence should be addressed. 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 acetylation 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 to 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.
Received March 31, 2006
Revised June 27, 2006
Accepted June 30, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Inherited variation in carcinogen-metabolizing enzymes and risk of colorectal polyps
Ellen L. Goode 1 *, John D. Potter 2, William R. Bamlet 3, David N. Rider 3, and Jeannette Bigler 4
2 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA
3 Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
4 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Ellen L. Goode, E-mail: egoode{at}mayo.edu
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