title: Melanoma risk is associated with vitamin D receptor gene polymorphisms.
abstract: Previous studies have reported that vitamin D receptor (VDR) gene polymorphisms are associated with the occurrence of various cancers, including melanoma. The aim of the current study was to investigate the association of VDR gene polymorphisms with melanoma risk, clinicopathological characteristics, and vitamin D levels. The study group included 117 patients (84 patients with superficial spreading melanoma and 33 patients with nodular melanoma). The control group included 122 sex-matched and age-matched healthy-blood donors of the same ethnicity. VDR gene polymorphisms FokI, EcoRV, TaqI, and ApaI were genotyped by real-time PCR. In 60 patients, the total 25-hydroxyvitamin D levels were evaluated in serum samples by direct chemiluminescence. Associations among parameters were considered to be significant if the P value was less than 0.05. Significant differences in the frequencies of VDR genotypes were observed between cases and the control group for FokI and TaqI polymorphisms (P<0.0001; P=0.005, respectively). Heterozygous Ff as well as mutant FF genotypes of the FokI polymorphism were associated with increased melanoma risk compared with the wild-type form [odds ratio (OR)=3.035, P=0.003; OR=9.276, P<0.0001, respectively]. A significantly increased melanoma risk was observed for the heterozygous Tt (OR=2.302, P=0.011) and the mutated variant tt (OR=3.697, P=0.003) of the TaqI polymorphism in comparison with the wild-type genotype. None of the polymorphisms studied was associated with clinicopathological characteristics and vitamin D serum level. Our results suggest that FokI and TaqI polymorphisms in the VDR gene may be considered as potential biomarkers for melanoma susceptibility. Low vitamin D levels in melanoma patients indicate the need for vitamin D supplementation.
authors.affiliation: aLaboratory for Molecular Genetics, Institute for Medical Research bClinic for Dermatovenereology cCenter for Biochemistry dClinic for Plastic Surgery and Burns, Military Medical Academy eFaculty of Medicine, Military Medical Academy, University of Defense fDepartment of Genetics and Evolution, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Zeljic
authors.forename: Lidija
authors.initials: L
authors.lastname: Kandolf-Sekulovic
authors.forename: Gordana
authors.initials: G
authors.lastname: Supic
authors.forename: Janko
authors.initials: J
authors.lastname: Pejovic
authors.forename: Marijan
authors.initials: M
authors.lastname: Novakovic
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Mijuskovic
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Magic
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D018167:Receptors, Calcitriol / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000097:blood / Q000235:genetics*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D014807:Vitamin D; C104450:25-hydroxyvitamin D