Association between vitamin D and ovarian cancer development in BRCA1 mutation carriers
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Tanja Pejovic1, Sonali Joshi1, Shawn Campbell1,2, Sarah Thisted1,3, Fuhua Xu2 and Jing Xu2,4
1 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA
2 Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA
3 Present address: College of Health and Human Services, Northern Arizona University, Flagstaff, Arizona, USA
4 Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA
Keywords: epithelial ovarian cancer;
Received: September 21, 2020 Accepted: October 27, 2020 Published: November 10, 2020
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 (BRCA1mut) 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 BRCA1mut and without BRCA1 mutations (BRCAwt). 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 BRCA1mut carriers were cultured with or without calcitriol supplementation for 72 hrs. VDR protein levels, cell proliferation and cell viability were analyzed.
Results: BRCA1mut women had lower serum calcifediol levels compared to BRCAwt women (p = 0.003). VDR protein expression was evident in ovarian and the fallopian tube epithelium of BRCAwt patients, but was reduced in BRCA1mut women. Calcitriol (biologically active VD) supplementation elevated VDR expression in cultured BRCA1mut 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 BRCA1mut women. VD treatment may limit BRCA1mut epithelial cell proliferation without affecting cell viability, providing a rationale for exploring the potential for VD in ovarian cancer prevention in BRCA1mut carriers.
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