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.
Type
Journal articleSubject
HumansPancreatic Neoplasms
Genetic Predisposition to Disease
Proto-Oncogene Proteins c-sis
Case-Control Studies
Genotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Aged
Middle Aged
Female
Male
Crk-Associated Substrate Protein
Genetic Variation
Genome-Wide Association Study
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https://hdl.handle.net/10161/18515Published Version (Please cite this version)
10.1002/ijc.31171Publication Info
Duan, Bensong; Hu, Jiangfeng; Liu, Hongliang; Wang, Yanru; Li, Hongyu; Liu, Shun;
... Wei, Qingyi (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.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.
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Show full item recordScholars@Duke
James Abbruzzese
D. C. I. Distinguished Professor of Medical Oncology
My research interests include the clinical study and treatment of pancreatic cancer.
Herbert Ira Hurwitz
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
Kouros Owzar
Professor of Biostatistics & Bioinformatics
cancer pharmacogenomicsdrug induced neuropathy, neutropenia and hypertensionstatistical
genetics statistical methods for high-dimensional data copulas survival analysis statistical
computing
Qingyi Wei
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
Jichun Xie
Associate Professor of Biostatistics & Bioinformatics
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