APC Asp1822Val and Gly2502Ser Polymorphisms and Risk of Colorectal Cancer and Adenoma
- Departments of 1Epidemiology and 2Nutrition and 3Program in Genetic and Molecular Epidemiology, Harvard School of Public Health; and 4Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Requests for reprints:
Gregory J. Tranah, Department of Epidemiology Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115. Phone: 617-525-2718; Fax: 617-432-1722. E-mail: gtranah{at}hsph.harvard.edu
Abstract
Mutation of the adenomatous polyposis coli (APC) tumor suppressor gene is an important initiating factor in the early stages of the adenoma-carcinoma sequence. The aim of this study was to investigate the two most common APC variants (Asp1822Val and Gly2502Ser) and their association with colorectal cancer and adenoma and whether these relationships are influenced by dietary and lifestyle factors. We analyzed 556 adenoma cases and 557 matched controls and 197 cancer cases and 490 matched controls nested within the Nurses' Health Study cohort, 274 cancer cases and 456 matched controls nested within the Physicians' Health Study cohort, and 375 adenoma cases and 724 matched controls nested within the Health Professionals Follow-up Study cohort. APC Asp1822Val and Gly2502Ser polymorphisms were not associated with risk of colorectal cancer or adenoma. For colorectal cancer, a significant interaction was found between Asp1822Val genotype and postmenopausal hormone (PMH) use among postmenopausal women (Pinteraction = 0.03). Current PMH use was associated with reduced risk overall and a statistically significant lower risk of colorectal cancer among carriers of one or two copies of the APC 1822Val allele (relative risk, 0.46; 95% confidence interval, 0.24-0.88) relative to wild-type never or past PMH users. Our results suggest that cigarette smoking, alcohol intake, and family history of colorectal cancer were positively associated and regular aspirin intake was inversely associated with colorectal adenoma in men and women. No gene-environment interactions were observed with these risk factors or with other dietary risk factors previously hypothesized to interact with the APC Asp1822Val polymorphism.
Footnotes
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Grant support: NIH research grants CA70817, CA87969, CA55075, CA42812, CA58684, and CA90598 and training grant CA 09001-27 (G.J. Tranah).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted December 29, 2004.
- Received September 17, 2004.
- Revision received December 17, 2004.
