Association of Vitamin D Receptor Gene Polymorphisms With Melanoma Risk: A Meta-analysis and Systematic Review

Abstract

Background/Aim: Increasing evidence indicates a relevance of the vitamin D endocrine system for pathogenesis of malignant melanoma. We performed a systematic review and meta-analysis to update previous reports that investigated the association between vitamin D receptor (VDR) gene polymorphisms and melanoma risk. Materials and Methods: A comprehensive literature search (PubMed, ISI Web of Science) identified a total of 14 studies that were eligible for inclusion in our meta-analysis. In the statistical analysis, the ORs and the 95% CIs were calculated for the dominant and recessive models for seven VDR gene polymorphisms, namely rs2228570 (FokI), rs731236 (TaqI), rs1544410 (BsmI), rs4516035 (A-1012G), rs11568820 (Cdx2), rs7975232 (ApaI) and rs739837 (BglI). Results were illustrated in Forest Plots. Publication bias was tested using Funnel Plots and the Egger's test. Results: Our meta-analysis showed in the dominant model (Bb + BB vs. bb) a significant association of a 15% risk reduction in malignant melanoma incidence for carriers of the rarer allele B of rs1544410 (Bsml). Notably, the dominant model (Ff + ff vs. FF) of rs2228570 (FokI) demonstrates that carriers of the rarer allele f are 22% more likely to develop malignant melanoma. For rs7975232 (ApaI), there is a 20% higher risk of melanoma for carriers of the rarer a allele (Aa + aa vs. AA). The results of the meta-analysis revealed no significant association between melanoma risk and the other investigated VDR polymorphisms. Conclusion: The VDR variants FokI, ApaI and BsmI may influence the susceptibility to developing melanoma. These findings support the concept, that the vitamin D endocrine system is of importance for pathogenesis of malignant melanoma.