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Potential Functional Variants in SMC2 and TP53 in the AURORA Pathway Genes and Risk of Pancreatic Cancer.

dc.contributor.author Feng, Yun
dc.contributor.author Liu, Hongliang
dc.contributor.author Duan, Bensong
dc.contributor.author Liu, Zhensheng
dc.contributor.author Abbruzzese, James
dc.contributor.author Walsh, Kyle M
dc.contributor.author Zhang, Xuefeng
dc.contributor.author Wei, Qingyi
dc.date.accessioned 2019-05-01T18:12:24Z
dc.date.available 2019-05-01T18:12:24Z
dc.date.issued 2019-02-22
dc.identifier 5363777
dc.identifier.issn 0143-3334
dc.identifier.issn 1460-2180
dc.identifier.uri https://hdl.handle.net/10161/18494
dc.description.abstract The AURORA pathway participates in mitosis and cell division, and alterations in mitosis and cell division can lead to carcinogenesis. Therefore, genetic variants in the AURORA pathway genes may be associated with susceptibility to pancreatic cancer. To test this hypothesis, we used three large, publically available pancreatic cancer genome-wide association studies (GWASs) datasets (PanScan I, II/III and PanC4) to assess the associations of 7,168 single nucleotide polymorphisms (SNPs) in a set of 62 genes of this pathway with pancreatic cancer risk (8,477 cases and 6,946 controls of European ancestry). We identify 15 significant pancreatic cancer risk-associated SNPs in three genes (SMC2, ARHGEF7 and TP53) after correction for multiple comparisons by a false discovery rate (FDR) < 0.20. Through further linkage disequilibrium analysis, SNP functional prediction and stepwise logistic regression analysis, we focused on three SNPs: rs3818626 in SMC2, rs79447092 in ARHGEF7 and rs9895829 in TP53. We found that these three SNPs were associated with pancreatic cancer risk [odds ratio (OR) = 1.12, 95% confidence interval (CI) = 1.07-1.17 and P = 2.20E-06 for the rs3818626 C allele; OR = 0.76, CI = 0.66-0.88 and P = 1.46E-04 for the rs79447092 A allele; and OR = 0.82, CI = 0.74-0.91 and P = 1.51E-04 for the rs9895829 G allele]. Their joint effect as the number of protective genotypes (NPGs) also showed a significant association with pancreatic cancer risk (trend test P ≤ 0.001). Finally, we performed an eQTL analysis and found that rs3818626 and rs9895829 were significantly associated with SMC2 and TP53 mRNA expression levels in 373 lymphoblastoid cell lines, respectively. In conclusion, these three representative SNPs may be potentially susceptibility loci for pancreatic cancer and warrant additional validation.
dc.language eng
dc.publisher Oxford University Press (OUP)
dc.relation.ispartof Carcinogenesis
dc.relation.isversionof 10.1093/carcin/bgz029
dc.subject AURORA
dc.subject pancreatic cancer susceptibility
dc.subject pathway analysis
dc.subject single nucleotide polymorphism
dc.title Potential Functional Variants in SMC2 and TP53 in the AURORA Pathway Genes and Risk of Pancreatic Cancer.
dc.type Journal article
duke.contributor.id Liu, Zhensheng|0633329
duke.contributor.id Abbruzzese, James|0634557
duke.contributor.id Walsh, Kyle M|0429230
duke.contributor.id Zhang, Xuefeng|0622096
duke.contributor.id Wei, Qingyi|0632334
dc.date.updated 2019-05-01T18:12:23Z
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Population Health Sciences
pubs.organisational-group Basic Science Departments
pubs.organisational-group Pathology
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Neurosurgery
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Medicine
pubs.publication-status Published
duke.contributor.orcid Walsh, Kyle M|0000-0002-5879-9981
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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