Estrogen Bioactivation, Genetic Polymorphisms, and Ovarian Cancer
- Thomas A. Sellers1,
- Joellen M. Schildkraut2,
- V. Shane Pankratz3,
- Robert A. Vierkant3,
- Zachary S. Fredericksen3,
- Janet E. Olson3,
- Julie Cunningham4,
- William Taylor4,
- Mark Liebow5,
- Carol McPherson1,
- Lynn C. Hartmann6,
- Tuya Pal1 and
- Araba A. Adjei7
- 1Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; 2Department of Community and Family Medicine and the Duke Comprehensive Cancer Center, Duke University, Durham, North Carolina; and Departments of 3Health Sciences Research, 4Laboratory Medicine and Pathology, 5Medicine, 6Medical Oncology, and 7Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota
- Requests for reprints:
Thomas A. Sellers, Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33602. Phone: 813-632-1315; Fax: 813-632-1334. E-mail: sellerta{at}moffitt.usf.edu
Abstract
Recent experimental evidence has shown that catechol estrogens can be activated through metabolism to form depurinating DNA adducts and thereby initiate cancer. Limited data are available regarding this pathway in epithelial ovarian cancer. We conducted a case-control study of 503 incident epithelial ovarian cancer cases at the Mayo Clinic in Rochester, MN, and Jacksonville, FL, and a 48-county region in North Carolina. Six hundred nine cancer-free controls were frequency matched to the cases on age, race, and residence. After an interview to obtain data on risk factors, a sample of blood was collected for DNA isolation. Subjects were genotyped for seven common single nucleotide polymorphisms in four genes involved in catechol estrogen formation (CYP1A1 and CYP1B1) or conjugation (COMT and SULT1A1). Data were analyzed using logistic regression, stratified by race, and with adjustment for design factors and potential confounders. None of the individual genotypes were significantly associated with ovarian cancer risk. However, an oligogenic model that considered the joint effects of the four candidate genes provided evidence for an association between combinations of these genes and ovarian cancer status (P = 0.015). Although preliminary, this study provides some support for the hypothesis that low-penetrance susceptibility alleles may influence risk of epithelial ovarian cancer.
- epidemiology
- case-control
- single nucleotide polymorphism
- catechol estrogen
- risk factor
- ovarian cancer
Footnotes
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Grant support: National Cancer Institute grant R01 CA88868.
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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 September 9, 2005.
- Received March 2, 2005.
- Revision received September 1, 2005.
