The steroid hormone 1,25 dihydroxyvitamin D3 is thought to protect against breast cancer. Its actions are mediated via the vitamin D receptor (VDR) and a number of polymorphisms in the VDR gene have been identified, some of which may alter susceptibility to breast cancer. This study has investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in a UK Caucasian population. Female breast cancer patients (n = 313) and control women with a negative screening mammogram (n = 410) were recruited and their VDR polymorphisms were determined. The 3' VDR polymorphism BsmI was significantly associated with breast cancer risk; odds ratio bb vs. BB genotype = 1.79 (95% CI, 1.12-2.86; P = 0.0221). In addition, over 70% of seven commonly used breast cancer cell lines were found to have the at-risk genotype bb. The 5' FokI gene variant was not associated with breast cancer risk. Further investigations into how these different genotypes may affect the functional mechanisms of the VDR will provide a better strategy for identifying women at risk of breast cancer and for developing improved treatments.
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