Variants Fok1 and Bsm1 on VDR are associated with the melanoma risk: evidence from the published epidemiological studies

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.