Vitamin D receptor polymorphisms and breast cancer risk in a large population-based case-control study of Caucasian and African-American women

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Abstract
Introduction: The involvement of vitamin D receptor (VDR), which is a key mediator in the vitamin D pathway, in breast cancer etiology has long been of interest. Methods: We examined the association between polymorphisms in the 3' end of the VDR gene, specifically BsmI and Poly(A), and breast cancer risk within a large, population-based, case-control study of breast cancer. Cases (n = 1,631) were Caucasian and African-American women, aged 35 to 64 years, who were diagnosed with incident, invasive breast cancer between July 1994 and April 1998. Control individuals (n = 1,435) were women without breast cancer ascertained through random digit dialing. Results: Accounting for age, study site, and sampling weights, we observed a significantly increased risk for breast cancer among Caucasian, postmenopausal carriers of the bb genotype of BsmI (odds ratio = 1.53, 95% confidence interval = 1.04 to 2.27). However, no associations with the bb genotype were observed in African-American women. Overall, there were no significant associations between the Poly(A) genotype and breast cancer risk in either racial group. Smoking status (ever/never) modified the association between both the BsmI and Poly(A) genotypes and breast cancer risk. The respective associations between these genotypes and breast cancer risk did not significantly vary by oral contraceptive use, hormone replacement therapy, or body mass index. Conclusion: Our results provide additional support for an increased risk for breast cancer in postmenopausal Caucasian women with the BsmI bb genotype and shed light on possible differential effects by menopausal status and race.