Objective: Studies on the relationship between vitamin D receptor (VDR) polymorphisms and Prostate Cancer (PCa) have shown conflicting results. Therefore, we conducted a meta-analysis of case-control studies to investigate a possible association between VDR (single-nucleotide polymorphisms) SNPs and PCa risk.

Materials and Methods: Our aim was to evaluate separately how the 6 known VDR gene SNPs TaqI (T>C), FokI (C>T), BsmI (G>A), Cdx2 (G>A), ApaI (G>T) and Poly-A (L/S) affect PCa in the general population and in ethnic subgroups of prostate cancer patients. Databases including Medline, Scopus, and Web of Science were searched. Studies meeting the inclusion criteria were reviewed in an updated meta-analysis using Revman 5.4.1 and Stata 16.0 software. The methodological quality of each study was assessed using the Newcastle-Ottawa scale. Fixed or random effect models were used to summarize odds ratios (ORs) with 95% CIs according to heterogeneity. Sensitivity analyses and meta-regression analyses were performed to identify potential sources of heterogeneity.

Results: A total of 65 studies fulfilled the inclusion criteria. The overall results indicated a positive association between Poly-A polymorphism and PCa risk, especially in the Caucasian population. However, in subgroup analysis by ethnicity, TaqI polymorphism was associated with increased risk of PCa in the Caucasian and Arab subgroups under the contrasting allelic and dominant genetic models. For ApaI polymorphism, our results show a significant positive association with PCa risk in Caucasian and Asian men under additive and recessive genetic models, respectively. Notably, the recessive, dominant and contrasting allelic models of the FokI polymorphism show a higher risk of developing PCa in Caucasian and mixed men, respectively. Conversely, the Cdx2 and BsmI polymorphisms showed no apparent association with PCa risk either in the overall results or in the subgroup analysis by ethnicity.

Conclusions: The results suggest that the VDR gene TaqI (T>C), FokI (C>T), ApaI (G>T), and Poly-A (L/S) SNPs are associated with PCa risk. Further large and well-designed studies are needed to confirm this conclusion.