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Vitamin D receptor polymorphisms in patients with cutaneous melanoma

Citation

Orlow, I and Roy, P and Reiner, AS and Yoo, S and Patel, H and Paine, S and Armstrong, BK and Kricker, A and Marrett, LD and Millikan, RC and Thomas, NE and Gruber, SB and Anton-Culver, H and Rosso, S and Gallagher, RP and Dwyer, T and Kanetsky, PA and Busam, K and From, L and Begg, CB and Berwick, M, GEM Study Group, Vitamin D receptor polymorphisms in patients with cutaneous melanoma, International Journal of Cancer, 130, (2) pp. 405-418. ISSN 0020-7136 (2012) [Refereed Article]

Copyright Statement

Copyright 2011 UICC

DOI: doi:10.1002/ijc.26023

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 single nucleotide polymorphisms (SNPs) in a large international multicenter population-based case-control study of melanoma. Buccal DNAs were obtained from 1,207 people with incident multiple primary melanoma and 2,469 with incident single primary melanoma. SNPs with known or suspected impact on VDR activity, haplotype tagging SNPs with ≥10% minor allele frequency 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 six polymorphisms: rs10875712 (odds ratios [OR] 1.28; 95% confidence interval (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) and rs1544410 (OR 1.30; 95%CI, 1.04-1.63); for two polymorphisms, homozygous carriers had a decreased risk: rs7305032 (OR 0.81; 95%CI 0.65-1.02) and rs7965281 (OR, 0.78; 95%CI, 0.62-0.99). We recognize the potential false positive findings because of multiple comparisons; however, the eight significant SNPs in our study outnumbered the two significant tests expected to occur by chance. The VDR may play a role in melanomagenesis.

Item Details

Item Type:Refereed Article
Keywords:VDR, SNP, melanoma, polymorphism, vitamin D
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Oncology and carcinogenesis not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Dwyer, T (Professor Terry Dwyer)
ID Code:82696
Year Published:2012
Web of Science® Times Cited:52
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-02-13
Last Modified:2017-11-02
Downloads:0

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