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

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Wang, Xiaomeng

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Liu, Hongliang

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Xu, Yinghui

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Xie, Jichun

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Zhu, Dakai

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Amos, Christopher I

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Fang, Shenying

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Lee, Jeffrey E

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Li, Xin

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Nan, Hongmei

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Song, Yanqiu

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Wei, Qingyi

dc.date.accessioned

2019-05-01T18:14:22Z

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2019-05-01T18:14:22Z

dc.date.issued

2018-12-29

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2019-05-01T18:14:22Z

dc.description.abstract

Remodeling or deregulation of the calcium signaling pathway is a relevant hallmark of cancer including cutaneous melanoma (CM). In the present 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, 1,830 SNPs were found to be significantly associated with CM-specific survival (CMSS) (P ≤ 0.050 and false-positive report probability ≤ 0.2), of which nine 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 (HR) of 1.52 [95% confidence interval (CI) = 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 (eQTL) 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.

dc.identifier

5266793

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0143-3334

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1460-2180

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https://hdl.handle.net/10161/18497

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eng

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Oxford University Press (OUP)

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Carcinogenesis

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10.1093/carcin/bgy188

dc.title

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

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Journal article

duke.contributor.orcid

Xie, Jichun|0000-0001-5905-6728

duke.contributor.orcid

Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439

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School of Medicine

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Duke

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Biostatistics & Bioinformatics

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Basic Science Departments

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Duke Cancer Institute

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Institutes and Centers

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Population Health Sciences

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Medicine, Medical Oncology

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Medicine

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Clinical Science Departments

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