Vitamin D receptor polymorphisms in patients with cutaneous melanoma

Abstract

The vitamin D receptor (VDR) gene has been associated with cancer risk, but only a few polymorphisms have been studied in relation to melanoma risk and the results have been inconsistent. We examined 38 VDR gene SNPs in a large international multi-center population-based case-control study of melanoma. Buccal DNAs were obtained from 1207 people with incident multiple primary melanoma and 2469 with incident single primary melanoma. SNPs with known or suspected impact on VDR activity, htSNPs with ≥10% MAF in Caucasians, and SNPs reported as significant in other association studies were examined. Logistic regression was used to calculate the relative risks conferred by the individual SNP. Eight of 38 SNPs in the promoter, coding, and 3’ gene regions were individually significantly associated with multiple primary melanoma after adjusting for covariates. The estimated increase in risk for individuals who were homozygous for the minor allele ranged from 25% to 33% for 6 polymorphisms: rs10875712 (OR 1.28; 95%CI, 1.01–1.62), rs4760674 (OR 1.33; 95% CI, 1.06–1.67), rs7139166 (OR 1.26; 95%CI, 1.02–1.56), rs4516035 (OR 1.25; 95%CI, 1.01–1.55), rs11168287 (OR 1.27; 95%CI, 1.03–1.57), rs1544410 (OR 1.30; 95%CI, 1.04–1.63); for 2 polymorphisms, homozygous carriers had a decreased risk: rs7305032 (OR 0.81; 95%CI 0.65–1.02), rs7965281 (OR, 0.78; 95%CI, 0.62–0.99). We recognize the potential false positive findings due to multiple comparisons; however the 8 significant SNPs in this study outnumbered the 2 significant tests expected to occur by chance. The vitamin D receptor may play a role in melanomagenesis.

Relationship between vitamin D receptor (VDR) polymorphisms and the efficacy of recombinant human growth hormone (rhGH) treatment in children with idiopathic short stature

“…Cdx-2 is differentially expressed in normal stomach and intestinal tissue, and is known to decrease progressively in patients with gastric intestinal metaplasia, dysplasia, and cancer. Moreover, Cdx-2 expression is associated with bone mineral density and susceptibility to fractures in the elderly (Orlow et al, 2012). Cdx-2 polymorphism is located in the DNA-binding portion of the gene, and therefore likely influences other transcriptional processes; polymorphisms in the VDR gene promoter region are important for the regulation of calcium absorption (Rowland et al, 2012).…”

The Polymorphisms in the Vitamin D Receptor Gene and Disease Severity in Sickle Cell Disease

“…It is located in the regulatory region UTR + 3713: Chr position 45262658 as per dbSNP (HuRef). It was found to be associated with reduced risk for cutaneous melanoma in a large population [13]. In a marker report, a trend analysis was done with this SNP and an association with systolic blood pressure was found in a British population, with an adjusted p value of 0.029.…”

“…In a marker report, a trend analysis was done with this SNP and an association with systolic blood pressure was found in a British population, with an adjusted p value of 0.029. More work is being currently done on this particular SNP (personal communication with Dr. Orlow [13]). …”

Vitamina D – Perspetivas Atuais

“…Apresenta também um efeito inibidor sobre a migração, invasão e metastização dos melanomas em ratos após administração sistémica. [54][55][56] No ser humano não há consenso sobre a recomendação de suplementação e níveis ótimos de vitamina D nos doentes com melanoma ou em risco de o desenvolver, no entanto uma revisão sugere manter níveis de 28-40ng/mL em doentes com melanoma, pelos efeitos moduladores da proliferação celular demonstrados in vitro. 57 Nas dermatoses fotossensíveis, a evicção solar restritiva é um fator de risco para hipovitaminose D. A deficiência de vitamina D em doentes com lúpus eritematoso sistémico é altamente prevalente, resultado de: evicção solar, fotoproteção, insuficiência renal e uso prolongado de medicação que altera o seu metabolismo.…”