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

Xiaomeng Wang, Hongliang Liu, Yinghui Xu, Jichun Xie, Dakai Zhu, Christopher I. Amos, Shenying Fang, Jeffrey E. Lee, Xin Li, Hongmei Nan, Yanqiu Song, Qingyi Wei

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalCarcinogenesis
Volume40
Issue number2
DOIs
StatePublished - Apr 29 2019

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Calcium Signaling
Single Nucleotide Polymorphism
Melanoma
Skin
Survival
Genome-Wide Association Study
Genes
Genotype
Quantitative Trait Loci
Skin Neoplasms
Meta-Analysis
Biomarkers
Confidence Intervals
Gene Expression
Messenger RNA
Neoplasms

ASJC Scopus subject areas

  • Cancer Research

Cite this

Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival. / Wang, Xiaomeng; Liu, Hongliang; Xu, Yinghui; Xie, Jichun; Zhu, Dakai; Amos, Christopher I.; Fang, Shenying; Lee, Jeffrey E.; Li, Xin; Nan, Hongmei; Song, Yanqiu; Wei, Qingyi.

In: Carcinogenesis, Vol. 40, No. 2, 29.04.2019, p. 279-288.

Research output: Contribution to journalArticle

Wang, X, Liu, H, Xu, Y, Xie, J, Zhu, D, Amos, CI, Fang, S, Lee, JE, Li, X, Nan, H, Song, Y & Wei, Q 2019, 'Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival', Carcinogenesis, vol. 40, no. 2, pp. 279-288. https://doi.org/10.1093/carcin/bgy188
Wang, Xiaomeng ; Liu, Hongliang ; Xu, Yinghui ; Xie, Jichun ; Zhu, Dakai ; Amos, Christopher I. ; Fang, Shenying ; Lee, Jeffrey E. ; Li, Xin ; Nan, Hongmei ; Song, Yanqiu ; Wei, Qingyi. / Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival. In: Carcinogenesis. 2019 ; Vol. 40, No. 2. pp. 279-288.
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abstract = "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.",
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AB - 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.

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