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.
Melanoma Res. 2014 Jun;24(3):273-9. 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.
先前的研究报告称，维生素 D 受体（VDR）基因多态性与多种癌症的发生有关，包括黑色素瘤。本研究旨在探讨 VDR 基因多态性与黑色素瘤风险、临床病理特征和维生素 D 水平的关系。研究组包括 117 例患者（84 例浅表扩散性黑色素瘤和 33 例结节性黑色素瘤）。对照组包括 122 名性别和年龄匹配的同种族健康献血者。采用实时 PCR 法对 VDR 基因多态性 FokI、EcoRV、TaqI 和 ApaI 进行基因分型。在 60 例患者中，通过直接化学发光法检测血清样本中的总 25-羟维生素 D 水平。如果 P 值小于 0.05，则认为参数之间存在关联。病例组和对照组在 FokI 和 TaqI 多态性中观察到 VDR 基因型的频率存在显著差异（P<0.0001；P=0.005）。与野生型相比，FokI 多态性的杂合性 Ff 以及突变性 FF 基因型与黑色素瘤风险增加相关[比值比（OR）=3.035，P=0.003；OR=9.276，P<0.0001]。与野生型相比，TaqI 多态性的杂合性 Tt（OR=2.302，P=0.011）和突变性 tt（OR=3.697，P=0.003）与黑色素瘤风险显著增加相关。研究中没有发现任何多态性与临床病理特征和维生素 D 血清水平相关。我们的结果表明，VDR 基因中的 FokI 和 TaqI 多态性可以被认为是黑色素瘤易感性的潜在生物标志物。黑色素瘤患者维生素 D 水平较低表明需要补充维生素 D。
