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


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.






Published Version (Please cite this version)


Publication Info

Wang, Xiaomeng, Hongliang Liu, Yinghui Xu, Jichun Xie, Dakai Zhu, Christopher I Amos, Shenying Fang, Jeffrey E Lee, et al. (2018). Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival. Carcinogenesis. 10.1093/carcin/bgy188 Retrieved from

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.



Jichun Xie

Associate Professor of Biostatistics & Bioinformatics

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.