Genetic Variants in the Platelet-Derived Growth Factor Subunit B Gene Associated with Pancreatic Cancer Risk

Abstract

The PDGF signaling pathway plays important roles in development and progression of human cancers. In this study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer risk in European populations by using three published GWAS datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed by using data from the 1000 Genomes, TCGA and GTEx projects. As a result, we identified two potential susceptibility loci (rs5757573 and rs6001516) of PDGFB associated with pancreatic cancer risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16, and P = 4.70x10⁻⁵ for the rs5757573 C allele and 1.21, 1.11-1.32, and 2.01x10⁻⁵ for the rs6001516 T allele]. Haplotype analysis revealed that the C-T haplotype carriers had a significantly increased risk of pancreatic cancer than those carrying the T-C haplotype (OR = 1.23, 95% CI = 1.12-1.34, P =5.00 × 10⁻⁶). The multivariate regression model incorporating the number of unfavorable genotypes (NUGs) with age and sex showed that carriers with 1-2 NUGs, particularly among 60-70 age group or males, had an increased risk of pancreatic cancer, compared with those without NUG. Further, the eQTL analysis revealed that both loci were correlated with a decreased mRNA expression level of PDGFB in lymphoblastoid cell lines and pancreatic tumor tissues (P = 0.015 and 0.071, respectively). Our results suggest that genetic variants in PDGFB may play a role in susceptibility to pancreatic cancer. Further population and functional validations of our findings are warranted. This article is protected by copyright. All rights reserved.

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