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.

Association of vdr, cyp27b1, cyp24a1 and mthfr gene polymorphisms with oral lichen planus risk

“…2-13.3) genes code for key enzymes involved in vitamin D anabolism and catabolism, 25-hydroxyvitamin D-1-hydroxylase and 25-hydroxyvitamin D-24-hydroxylase, respectively [11]. Identified polymorphisms in vitamin D related genes were extensively studied in relation to various types of diseases, such as cancer [14][15][16], autoimmune [17,18], and inflammatory diseases [19,20]. Our research group previously reported association between VDR and CYP24A1 gene polymorphisms with oral cancer risk and survival [21], while polymorphisms in these genes have not previously been investigated in OLP patients.…”

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

“…We identified 10 suitable studies with a total of 4,961 melanoma patients and 4,605 controls which have described associations between common VDR variants and melanoma risk (Table 1) [15-24]. The variants Apa1, Bsm1, Cdx2, EcoRV, Fok1, and Taq1 were each evaluated in at least three studies and were included in the current meta-analysis.…”

“…Of them, three were performed in the USA, three in UK, one in Spain, one in Italy, one in Poland, and one in Serbia. None of the included studies was derived from the HWE for genotype distribution in the controls, except for one study that was performed by the Zeljic et al [24], in which a significant difference in the frequency of Apa1 in control subjects was identified ( p  = .001). The study performed by Randerson-Moor et al [22].…”

“…Seven studies examined a total of 3,621 cases and 2,783 controls to determine the association between the EcoRV VDR variant and melanoma risk [17,18,20-24] (Table 1). No significant associations between the variant and melanoma risk were identified by the meta-analysis, with pooled ORs of 1.09 (95% CI = 0.93–1.27; Q = 11.40, df = 7, p  = .122; I 2  = 39%) for the GA vs. AA genotype and 1.09 (95% CI = 0.90–1.33; Q = 10.32, df = 7, p  = .182; I 2  = 32%) for the GG vs. AA genotype.…”

“…We identified eight eligible studies with a total of 4,189 cases and 4,084 controls that evaluated the association between the Fok1 VDR variant and melanoma risk [15,16,18-20,22-24] (Table 1). The pooled estimates indicated that an Ff genotype conferred an 18% increase in melanoma risk (pooled OR = 1.18, 95% CI = 1.06–1.30; Figure 3A), whereas ff lead to a 19% increased risk of melanoma (pooled OR = 1.19, 95% CI = 1.01–1.41; Figure 3B) when compared with those of the FF genotype.…”