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

OBJECTIVE

Women with inherited mutations in 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 mutation ( ) carriers. Therefore, we investigated VD levels and actions in cancer free women with mutations.

MATERIALS AND METHODS

Blood, ovary and fallopian tube samples were collected from healthy pre-menopausal women with and without BRCA1 mutations ( ). 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 carriers were cultured with or without calcitriol supplementation for 72 hrs. VDR protein levels, cell proliferation and cell viability were analyzed.

RESULTS

women had lower serum calcifediol levels compared to women ( = 0.003). VDR protein expression was evident in ovarian and the fallopian tube epithelium of patients, but was reduced in women. Calcitriol (biologically active VD) supplementation elevated VDR expression in cultured OSEs ( = 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 women. VD treatment may limit epithelial cell proliferation without affecting cell viability, providing a rationale for exploring the potential for VD in ovarian cancer prevention in carriers.