Associations Between Polymorphisms in the Vitamin D Receptor and Breast Cancer Risk
- Wendy Y. Chen1,2,
- Elizabeth R. Bertone-Johnson5,
- David J. Hunter1,3,
- Walter C. Willett1,3,4 and
- Susan E. Hankinson1,3
- 1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital; 2Department of Adult Oncology, Dana-Farber Cancer Institute; Departments of 3Epidemiology and 4Nutrition, Harvard School of Public Health, Boston; and 5Department of Public Health, University of Massachusetts, Amherst, Massachusetts
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Wendy Y. Chen, Channing Laboratory, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115. Phone: 617-525-2225; Fax: 617-525-2008. E-mail: wendy.chen{at}channing.hardvard.edu
Abstract
Biological and epidemiologic data suggest that vitamin D levels may influence breast cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D and additionally interacts with other cell-signaling pathways that influence cancer development. Because functional data exist on FOK1 and previous studies have suggested a relation between BSM1 and breast cancer risk, we evaluated the associations of the FOK1 and BSM1 VDR polymorphisms and breast cancer risk. In a case-control study nested within the Nurses' Health Study, we genotyped 1,234 incident cases (diagnosed between return of a blood sample in 1989-1990 and June 1, 2000) and 1,676 controls for FOK1, and 1,180 cases and 1,547 controls for BSM1. We observed a significantly increased risk of breast cancer among carriers of the ff genotype of FOK1 (multivariate odds ratio, 1.34; 95% confidence intervals, 1.06-1.69) compared with those with FF. We did not observe an association between polymorphisms in BSM1 and breast cancer risk (multivariate odds ratio, 0.93; 95% confidence intervals, 0.72-1.20) for BB versus bb). The FOK1 association did not vary significantly by menopausal status, estrogen, and progesterone receptor status of the tumors, or plasma levels of 25 hydroxyvitamin D or 1,25 dihydroxyvitamin D. Our results suggest that the VDR may be a mediator of breast cancer risk and could represent a target for cancer prevention efforts.
Footnotes
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Grant support: Public Health Services grants CA49449 and CA87969 from the National Cancer Institute, NIH.
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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 July 20, 2005.
- Received April 21, 2005.
- Revision received June 23, 2005.
