Genetic variants of PDGF signaling pathway genes predict cutaneous melanoma survival
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Hong Li1,2,3, Yanru Wang2,3, Hongliang Liu2,3, Qiong Shi2,3, Hongyu Li2,3, Wenting Wu4, Dakai Zhu5, Christopher I. Amos5, Shenying Fang6, Jeffrey E. Lee6, Yi Li7, Jiali Han4 and Qingyi Wei2,3,8
1Department of Clinical Laboratory, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China
2Duke Cancer Institute, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA
3Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
4Department of Epidemiology, Fairbanks School of Public Health, Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN 46202, USA
5Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA
6Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
7Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
8Department of Population Health Sciences, Duke University School of Medicine, Durham, NC 27710, USA
Qingyi Wei, email: email@example.com
Jiali Han, email: firstname.lastname@example.org
Keywords: cutaneous melanoma, PDGF signaling pathway, single nucleotide polymorphisms, Cox regression
Received: January 12, 2017 Accepted: July 24, 2017 Published: August 14, 2017
To investigate whether genetic variants of platelet-derived growth factor (PDGF) signaling pathway genes are associated with survival of cutaneous melanoma (CM) patients, we assessed associations of single-nucleotide polymorphisms in PDGF pathway with melanoma-specific survival in 858 CM patients of M.D. Anderson Cancer Center (MDACC). Additional data of 409 cases from Harvard University were also included for further analysis. We identified 13 SNPs in four genes (COL6A3, NCK2, COL5A1 and PRKCD) with a nominal P < 0.05 and false discovery rate (FDR) < 0.2 in MDACC dataset. Based on linkage disequilibrium, functional prediction and minor allele frequency, a representative SNP in each gene was selected. In the meta-analysis using MDACC and Harvard datasets, there were two SNPs associated with poor survival of CM patients: rs6707820 C>T in NCK2 (HR = 1.87, 95% CI = 1.35-2.59, Pmeta = 1.53E-5); and rs2306574 T>C in PRKCD (HR = 1.73, 95% CI = 1.33-2.24, Pmeta = 4.56E-6). Moreover, CM patients in MDACC with combined risk genotypes of these two loci had markedly poorer survival (HR = 2.47, 95% CI = 1.58-3.84, P < 0.001). Genetic variants of rs6707820 C>T in NCK2 and rs2306574 T>C in PRKCD of the PDGF signaling pathway may be biomarkers for melanoma survival.
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