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Melanoma risk is associated with vitamin D receptor gene polymorphisms

Zeljic, Katarinaa,f,*; Kandolf-Sekulovic, Lidijab,e,*; Supic, Gordanaa,e; Pejovic, Jankoc; Novakovic, Marijand,e; Mijuskovic, Zeljkob,e; Magic, Zvonkoa,e

doi: 10.1097/CMR.0000000000000065

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.

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

* Katarina Zeljic and Lidija Kandolf-Sekulovic contributed equally to the writing of this article.

All supplementary data is available directly from the corresponding author.

Correspondence to Katarina Zeljic, PhD, Laboratory for Molecular Genetics, Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11 000 Belgrade, Serbia Tel: +381 63 84 52 350; fax:+381 11 266 27 22; e-mails:,

Received December 30, 2013

Accepted February 11, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins