Vitamin D and melanoma: an umbrella meta-analysis of serum levels, dietary intake, and VDR polymorphisms

Vitamin D regulates immune function, cell proliferation, and differentiation, and may inhibit carcinogenesis. Both serum vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene have been linked to melanoma, but findings are inconsistent. This umbrella meta-analysis critically appraised existing evidence on vitamin D intake, serum concentration, and six VDR polymorphisms (FokI, BsmI, TaqI, ApaI, EcoRV, Cdx2) in relation to melanoma risk. PubMed, Scopus, and Web of Science were searched to November 2025 for meta-analyses examining vitamin D intake, serum concentration, or VDR polymorphisms and melanoma risk in adults. Eligible studies reported relative risks (RR) or odds ratios (OR) with 95% confidence intervals (CI). Methodological quality was assessed using AMSTAR 2. Pooled effect sizes were calculated using a random-effects model. Nine eligible meta-analyses comprising 63 datasets were included. The FokI polymorphism was significantly associated with increased melanoma risk (RR: 1.14; 95% CI: 1.10–1.18), whereas the BsmI polymorphism was associated with decreased risk (RR: 0.87; 95% CI: 0.81–0.93). No significant associations were observed for TaqI, ApaI, EcoRV, or Cdx2 polymorphisms. No significant associations were observed for serum vitamin D concentration or dietary vitamin D intake in relation to melanoma risk. Study quality ranged from critically low to high, with only two meta-analyses meeting high-quality criteria. This umbrella meta-analysis suggests that the VDR FokI polymorphism is associated with an increased risk of melanoma, whereas the BsmI polymorphism may confer a protective association. No significant associations were observed for TaqI, ApaI, EcoRV, or Cdx2 polymorphisms. However, the overall certainty of the evidence is limited by the generally low methodological quality of the included meta-analyses, necessitating cautious interpretation of these findings. Further well-designed, large-scale studies across diverse populations are required to validate these associations and clarify their clinical relevance.