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Associations Between Polymorphisms in the Vitamin D Receptor and Breast Cancer Risk

¹ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital; ² Department of Adult Oncology, Dana-Farber Cancer Institute; Departments of ³ Epidemiology and ⁴ Nutrition, Harvard School of Public Health, Boston; and ⁵ Department of Public Health, University of Massachusetts, Amherst, Massachusetts

Requests for reprints: 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

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.

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