Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.
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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.
Genetic Predisposition to Disease
Proto-Oncogene Proteins c-sis
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Crk-Associated Substrate Protein
Genome-Wide Association Study
Published Version (Please cite this version)10.1002/ijc.31171
Publication InfoXie, Jichun; Owzar, Kouros; Wei, Qingyi; Abbruzzese, James; Hurwitz, Herbert; Duan, Bensong; ... Gao, Hengjun (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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D. C. I. Professor of Medical Oncology
My research interests include the clinical study and treatment of pancreatic cancer.
Adjunct Professor in the Department of Medicine
Particular Clinical Interests and Skills: Phase I clinical trials involving new anti cancer drugs; drug combinations; and combinations of new drugs with radiation; cancers of the GI system
Professor of Biostatistics and Bioinformatics
cancer pharmacogenomicsdrug induced neuropathy, neutropenia and hypertensionstatistical genetics statistical methods for high-dimensional data copulas survival analysis statistical computing
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and
Associate Professor of Biostatistics & Bioinformatics
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