Show simple item record

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

dc.contributor.author Duan, Bensong
dc.contributor.author Hu, Jiangfeng
dc.contributor.author Liu, Hongliang
dc.contributor.author Wang, Yanru
dc.contributor.author Li, Hongyu
dc.contributor.author Liu, Shun
dc.contributor.author Xie, Jichun
dc.contributor.author Owzar, Kouros
dc.contributor.author Abbruzzese, James
dc.contributor.author Hurwitz, Herbert
dc.contributor.author Gao, Hengjun
dc.contributor.author Wei, Qingyi
dc.date.accessioned 2019-05-01T18:34:24Z
dc.date.available 2019-05-01T18:34:24Z
dc.date.issued 2018-04
dc.identifier.issn 0020-7136
dc.identifier.issn 1097-0215
dc.identifier.uri https://hdl.handle.net/10161/18515
dc.description.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.
dc.language eng
dc.publisher Wiley
dc.relation.ispartof International journal of cancer
dc.relation.isversionof 10.1002/ijc.31171
dc.subject Humans
dc.subject Pancreatic Neoplasms
dc.subject Genetic Predisposition to Disease
dc.subject Proto-Oncogene Proteins c-sis
dc.subject Case-Control Studies
dc.subject Genotype
dc.subject Polymorphism, Single Nucleotide
dc.subject Quantitative Trait Loci
dc.subject Aged
dc.subject Middle Aged
dc.subject Female
dc.subject Male
dc.subject Crk-Associated Substrate Protein
dc.subject Genetic Variation
dc.subject Genome-Wide Association Study
dc.title Genetic variants in the platelet-derived growth factor subunit B gene associated with pancreatic cancer risk.
dc.type Journal article
duke.contributor.id Xie, Jichun|0656801
duke.contributor.id Owzar, Kouros|0298315
duke.contributor.id Abbruzzese, James|0634557
duke.contributor.id Hurwitz, Herbert|0145800
duke.contributor.id Wei, Qingyi|0632334
dc.date.updated 2019-05-01T18:34:24Z
pubs.begin-page 1322
pubs.end-page 1331
pubs.issue 7
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Population Health Sciences
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 142
duke.contributor.orcid Xie, Jichun|0000-0001-5905-6728
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record