Vitamin D Pathway Related Polymorphisms And Vitamin D Receptor Expression In Breast Cancer

Vitamin D deficiency is an emerging risk factor for breast cancer suggesting its role in breast cancer pathogenesis. Recent evidence suggests vitamin D receptor (VDR) expression is a prognosis predictor in breast cancer. We set out to determine the status of VDR expression in histologically characterized breast cancers, and whether common genetic variants modify VDR expression in breast cancer. One-hundred and twenty Kuwaiti female breast cancer fixed tissues were assessed for VDR expression to identify the level and location of its expression by immunohistochemistry. VDR variants (rs731236, rs2228570), and vitamin D binding protein (VDBP) variants (rs4588, rs7041) genotypes were ascertained in breast cancer specimens using Taqman genotyping assays. VDR nuclear expression correlated with low grade tumors (p = 0.01), whereas cytoplasmic expression correlated with lymph node positive tumors (p = 0.03). Absence of VDR expression was a marker for high-grade dedifferentiated tumors (p = 0.01). VDBP rs7041 associated with breast cancer risk (OR 1.92, 95% CI: 1.34 - 2.73: p = 0.0004), and VDR rs2228570 correlated with increased VDR cytoplasmic expression (p < 0.0001). In conclusion, VDR expression is altered in breast cancer confirming its involvement in breast cancer progression. Genetic factors appear to play a role in breast cancer risk, and may modify tumor sensitization to vitamin D.