{"doi":"10.18632/oncotarget.27803","title":"Association between vitamin D and ovarian cancer development in BRCA1 mutation carriers","abstract":"// Tanja Pejovic 1 , Sonali Joshi 1 , Shawn Campbell 1 , 2 , Sarah Thisted 1 , 3 , Fuhua Xu 2 and Jing Xu 2 , 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 Correspondence to: Tanja Pejovic, email: pejovict@ohsu.edu Keywords: epithelial ovarian cancer; BRCA1 mutation carriers; vitamin D; cancer prevention Received: September 21, 2020     Accepted: October 27, 2020     Published: November 10, 2020 Copyright: © 2020 Pejovic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT 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.","journal":"Oncotarget","year":2020,"id":109604,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":522476,"name":"Sonali Joshi","orcid":"0000-0002-8847-2613","position":1,"is_corresponding":false},{"id":435037,"name":"Shawn Campbell","orcid":null,"position":2,"is_corresponding":false},{"id":523352,"name":"Sarah Thisted","orcid":null,"position":3,"is_corresponding":false},{"id":429374,"name":"Fuhua Xu","orcid":null,"position":4,"is_corresponding":false},{"id":428439,"name":"Jing Xu","orcid":"0000-0003-1116-6631","position":5,"is_corresponding":false},{"id":33071,"name":"Tanja Pejović","orcid":"0000-0001-8537-1086","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:12:50.712357Z","pmid":"33227068","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}