Several pre-clinical studies have identified the anti-proliferative effects of 25-hydroxyvitamin D (25(OH) D; vitamin D). Ultraviolet radiation (UVR) is essential for vitamin D synthesis yet increases the risk of melanoma. Observational studies on the association of vitamin D levels with melanoma risk have reported inconclusive results, and are difficult to interpret due to the potential confounding from the dual role of UVR.

Our objective was to determine whether there is a causal association between genetically predicted 25(OH) D concentrations and melanoma using a Mendelian randomization (MR) approach.

We performed MR using summary data from a large genome-wide association study (GWAS) meta-analysis of melanoma risk, consisting of 12,874 cases and 23,203 controls. Five SNPs that are associated with 25(OH) D concentration rs12785878, rs10741657, rs2282679, rs6013897 and rs116970203 were selected as instrumental variables (IVs). Inverse variance weighted method was used to access the evidence for causality. MR results from the melanoma meta-analysis were combined with results from an MR study based on a melanoma risk GWAS using UK Biobank data.

A 20 nmol/L decrease in 25(OH) D was not associated with melanoma risk (OR = 1.06, 95% CI = 0.94 - 1.19). Results from the UK Biobank were concordant with this, with meta-analysis of our and UK Biobank derived MR causal estimates showing no association (OR = 1.02, 95% CI = 0.92 - 1.13 for a 20nmol/L decrease).

Our study results suggest that the genetically vitamin D levels may not be causally associated with the risk of melanoma. This article is protected by copyright. All rights reserved.