Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.

Abstract

The platelet-derived growth factor (PDGF) signaling pathway plays important roles in development and progression of human cancers. In our study, we aimed to identify genetic variants of the PDGF pathway genes associated with pancreatic cancer (PC) risk in European populations using three published genome-wide association study datasets, which consisted of 9,381 cases and 7,719 controls. The expression quantitative trait loci (eQTL) analysis was also performed 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 PC risk [odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.05-1.16, and p = 4.70 × 10-5 for the rs5757573 C allele and 1.21, 1.11-1.32, and 2.01 × 10-5 for the rs6001516 T allele]. Haplotype analysis revealed that the C-T haplotype carriers had a significantly increased risk of PC 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 PC, compared to those without NUG. Furthermore, 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 PC. Further population and functional validations of our findings are warranted.

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Published Version (Please cite this version)

10.1002/ijc.31171

Publication Info

Duan, Bensong, Jiangfeng Hu, Hongliang Liu, Yanru Wang, Hongyu Li, Shun Liu, Jichun Xie, Kouros Owzar, et al. (2018). Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk. International journal of cancer, 142(7). pp. 1322–1331. 10.1002/ijc.31171 Retrieved from https://hdl.handle.net/10161/18515.

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Scholars@Duke

Xie

Jichun Xie

Associate Professor of Biostatistics & Bioinformatics
Owzar

Kouros Owzar

Professor of Biostatistics & Bioinformatics

cancer pharmacogenomics
drug induced neuropathy, neutropenia and hypertension
statistical genetics
statistical methods for high-dimensional data
copulas
survival analysis
statistical computing


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