TY - JOUR
T1 - Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival
AU - Wang, Xiaomeng
AU - Liu, Hongliang
AU - Xu, Yinghui
AU - Xie, Jichun
AU - Zhu, Dakai
AU - Amos, Christopher I.
AU - Fang, Shenying
AU - Lee, Jeffrey E.
AU - Li, Xin
AU - Nan, Hongmei
AU - Song, Yanqiu
AU - Wei, Qingyi
N1 - Publisher Copyright:
© The Author(s) 2018.
PY - 2019/4/29
Y1 - 2019/4/29
N2 - 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.
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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U2 - 10.1093/carcin/bgy188
DO - 10.1093/carcin/bgy188
M3 - Article
C2 - 30596980
AN - SCOPUS:85065486521
SN - 0143-3334
VL - 40
SP - 279
EP - 288
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -