Genetic variants of the vitamin D receptor gene alter risk of cutaneous melanoma

Sunlight causes DNA damage but also induces production of vitamin D whose metabolite 1,25-(OH)(2)D-3 has antiproliferative and pro-differentiative effects in both melanocytes and cutaneous melanoma (CM) cells mediated through the vitamin D receptor (VDR). We hypothesized that genetic polymorphisms of VDR are associated with risk of CM. In a hospital-based case-control study of 602 non-Hispanic white CM patients and 603 cancer-free control subjects frequency matched by age and sex, we genotyped two VDR polymorphisms (Taql and Fokl) and assessed their association with CM risk. We found that a significantly decreased risk was associated with VDR-Taql Tt (adjusted odds ratio (OR), 0.70; 95% confidence interval (0), 0.54-0.90) and Tt+ tt (OR = 0.70; 95% Cl, 0.55-0.89) genotypes, compared with the VDR-Taql TT genotype, whereas an increased risk was associated with VDR-Fokl Ff genotype (OR = 1.32; 95% Cl, 1.03-1.68), and a borderline significantly increased risk was associated with Ff + ff (OR = 1.26; 95% Cl, 1.00-1.59) genotypes, compared with the VDR-Fokl FF genotype. In conclusion, genetic variants (i.e., Taql t protective allele and Fokl f risk allele) in VDR may alter risk of CM.