Vitamin D receptor (VDR) variants are risk factors for ovarian cancer: a meta-analysis and trial sequential analysis

Abstract

The importance of Vitamin D in ovarian cancer (OC) has been well documented, and lower levels have been associated with susceptibility to OC. Vitamin D exerts its effect through the vitamin D receptor (VDR). Common genetic variants in the VDR gene (Fok I, TaqI, BamI and ApaI) have been linked with the susceptibility to the development of OC; however, the reports remain contradictory. To draw a valid conclusion, we performed a meta-analysis of the earlier published reports in the present study. The literature search was performed in PubMed, Google Scholar, and Scopus databases. All relevant articles were screened, and eligible reports were identified based on prefixed inclusion and exclusion criteria. Data such as author’s details, year of publication, ethnicity, genotype and allele prevalence in cases and controls were extracted from the eligible reports. The meta-analysis was performed using Comprehensive Meta-analysis Software (CMA) V3. Eight articles, including data from fourteen independent cohorts, comprised 4276 cases and 6739 healthy controls considered for the analysis. VDR FokI and BamI variants revealed a significant association with an increased risk of OC. Other VDR polymorphisms (TaqI and ApaI) failed to demonstrate such an association with OC. Interestingly, the sensitivity analysis revealed minimal deviation from the parent meta-analysis, supporting the robustness of the present analysis. The trial sequential analysis revealed the inclusion of a sufficient number of studies for FokI polymorphism. It highlighted the requirement for additional case-control studies in VDR (ApaI, BamI and TaqI) to draw a definitive conclusion. FokI and BamI polymorphisms are associated with susceptibility to OC.