Association between vitamin D and ovarian cancer development in BRCA1 mutation carriers

Objective: Women with inherited mutations in BRCA1 gene have a high (40–70%) genetic risk of developing ovarian cancer. Epidemiological studies suggest an inverse correlation between serum vitamin D (VD) levels and the risk of ovarian cancer, but there is a lack of data from BRCA1 mutation (BRCA1(mut)) carriers. Therefore, we investigated VD levels and actions in cancer free women with BRCA1 mutations. Materials and Methods: Blood, ovary and fallopian tube samples were collected from healthy pre-menopausal women with BRCA1(mut) and without BRCA1 mutations (BRCA(wt)). Serum calcifediol (major circulating form of VD) concentrations were measured by electrochemiluminescence immunoassay. Immunohistochemistry was performed on paraffin-embedded ovarian and fallopian tube sections to determine vitamin D receptor (VDR) expression. Ovarian surface epithelial cells (OSEs) from BRCA1(mut) carriers were cultured with or without calcitriol supplementation for 72 hrs. VDR protein levels, cell proliferation and cell viability were analyzed. Results: BRCA1(mut) women had lower serum calcifediol levels compared to BRCA(wt) women (p = 0.003). VDR protein expression was evident in ovarian and the fallopian tube epithelium of BRCA(wt) patients, but was reduced in BRCA1(mut) women. Calcitriol (biologically active VD) supplementation elevated VDR expression in cultured BRCA1(mut) OSEs (p = 0.005) and decreased cell proliferation rates in a dose-dependent manner without inducing apoptosis. Conclusions: VD biosynthesis and signaling via VDR in the ovarian and fallopian tube epithelium are impaired in BRCA1(mut) women. VD treatment may limit BRCA1(mut) epithelial cell proliferation without affecting cell viability, providing a rationale for exploring the potential for VD in ovarian cancer prevention in BRCA1(mut) carriers.