Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival.

Journal Article (Journal Article)

Remodeling or deregulation of the calcium signaling pathway is a relevant hallmark of cancer including cutaneous melanoma (CM). In this study, using data from a published genome-wide association study (GWAS) from The University of Texas M.D. Anderson Cancer Center, we assessed the role of 41,377 common single-nucleotide polymorphisms (SNPs) of 167 calcium signaling pathway genes in CM survival. We used another GWAS from Harvard University as the validation dataset. In the single-locus analysis, 1830 SNPs were found to be significantly associated with CM-specific survival (CMSS; P ≤ 0.050 and false-positive report probability ≤ 0.2), of which 9 SNPs were validated in the Harvard study (P ≤ 0.050). Among these, three independent SNPs (i.e. PDE1A rs6750552 T>C, ITPR1 rs6785564 A>G and RYR3 rs2596191 C>A) had a predictive role in CMSS, with a meta-analysis-derived hazards ratio of 1.52 (95% confidence interval = 1.19-1.94, P = 7.21 × 10-4), 0.49 (0.33-0.73, 3.94 × 10-4) and 0.67 (0.53-0.86, 0.0017), respectively. Patients with an increasing number of protective genotypes had remarkably improved CMSS. Additional expression quantitative trait loci analysis showed that these genotypes were also significantly associated with mRNA expression levels of the genes. Taken together, these results may help us to identify prospective biomarkers in the calcium signaling pathway for CM prognosis.

Full Text

Duke Authors

Cited Authors

  • Wang, X; Liu, H; Xu, Y; Xie, J; Zhu, D; Amos, CI; Fang, S; Lee, JE; Li, X; Nan, H; Song, Y; Wei, Q

Published Date

  • April 29, 2019

Published In

Volume / Issue

  • 40 / 2

Start / End Page

  • 279 - 288

PubMed ID

  • 30596980

Pubmed Central ID

  • PMC6487681

Electronic International Standard Serial Number (EISSN)

  • 1460-2180

Digital Object Identifier (DOI)

  • 10.1093/carcin/bgy188

Language

  • eng

Conference Location

  • England