title: 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 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.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. orlowi@mskcc.org
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.forename: Pampa
authors.initials: P
authors.lastname: Roy
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: Sarah
authors.initials: S
authors.lastname: Yoo
authors.forename: Himali
authors.initials: H
authors.lastname: Patel
authors.forename: Susan
authors.initials: S
authors.lastname: Paine
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
authors.forename: Anne
authors.initials: A
authors.lastname: Kricker
authors.forename: Loraine D
authors.initials: LD
authors.lastname: Marrett
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Thomas
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: Stefano
authors.initials: S
authors.lastname: Rosso
authors.forename: Richard P
authors.initials: RP
authors.lastname: Gallagher
authors.forename: Terence
authors.initials: T
authors.lastname: Dwyer
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Klaus
authors.initials: K
authors.lastname: Busam
authors.forename: Lynn
authors.initials: L
authors.lastname: From
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
mesh_terms: D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol