Genetic variants in the vitamin D pathway genes VDBP and RXRA modulate cutaneous melanoma disease-specific survival

Jieyun Yin, Hongliang Liu, Xiaohua Yi, Wenting Wu, Christopher I. Amos, Shenying Fang, Jeffrey E. Lee, Jiali Han, Qingyi Wei

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Single nucleotide polymorphisms (SNPs) in the vitamin D pathway genes have been implicated in cutaneous melanoma (CM) risk, but their role in CM disease-specific survival (DSS) remains obscure. We comprehensively analyzed the prognostic roles of 2669 common SNPs in the vitamin D pathway genes using data from a published genome-wide association study (GWAS) at The University of Texas M.D. Anderson Cancer Center (MDACC) and then validated the SNPs of interest in another GWAS from the Nurses' Health Study and Health Professionals Follow-up Study. Among the 2669 SNPs, 203 were significantly associated with DSS in MDACC dataset (P < 0.05 and false-positive report probability < 0.2), of which 18 were the tag SNPs. In the replication, two of these 18 SNPs showed nominal significance: the VDBP rs12512631 T > C was associated with a better DSS [combined hazards ratio (HR) = 0.66]; and the same for RXRA rs7850212 C > A (combined HR = 0.38), which were further confirmed by the Fine and Gray competing-risks regression model. Further bioinformatics analyses indicated that these loci may modulate corresponding gene methylation status.

Original languageEnglish (US)
Pages (from-to)176-185
Number of pages10
JournalPigment Cell and Melanoma Research
Volume29
Issue number2
DOIs
StatePublished - Mar 1 2016

Keywords

  • Cox regression
  • Cutaneous melanoma
  • Disease-specific survival
  • Single nucleotide polymorphisms
  • Vitamin D pathway

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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