Background: The vitamin D receptor (VDR) mediates the major cellular activities of vitamin D and regulates various signaling pathways implicated in cancer development and progression. VDR variants have been found associated with the risk of developing melanoma; however, previous epidemiological studies are inconsistent. We have systematically reviewed the published epidemiological literature and conducted a meta-analysis to assess associations between common VDR variants and melanoma risk.
Results: We identified 10 eligible studies that evaluated six VDR variants (Apa1, Bsm1, Cdx2, EcoRV, Fok1, and Taq1) in a total of 4,961 melanoma patients and 4,605 controls. The pooled estimates identified two variants-Fok1 and Bsm1-as significantly associated with melanoma risk, but not for the other four variants Apa1, Cdx2, EcorV and Taq1. For Fok1, the pooled OR was 1.18 (95% CI = 1.06-1.30; I(2) = 22%) for Ff vs. FF and 1.19 (95% CI = 1.01-1.41; I(2) = 0%) for ff vs. FF. The dominant genetic model suggested the allele f carriers showed an 18% (pooled OR = 1.18, 95% CI = 1.07-1.29; I(2) = 0%) increased risk for melanoma compared to homozygote FF. In contrast, the Bsm1 was found to be associated with a decreased risk for melanoma with the pooled OR was 0.85 (95% CI = 0.76-0.95; I(2) = 0%) for Bb vs. bb and 0.83 (95% CI = 0.68-1.00; I(2) = 28%) for BB vs. bb. Under the dominant genetic model, a 15% (pooled OR = 0.85, 95% CI = 0.76-0.94; I(2) = 0%) decrease of melanoma risk was found for those with BB or Bb genotype compared to those of bb genotype.
Conclusions: The VDR variants Fok1 and Bsm1 may influence the susceptibility to developing melanoma, though further studies are needed to verify these conclusions.