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Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk. Zhao, Lingling Liu, Hongliang Luo, Sheng Moorman, Patricia G Walsh, Kyle M Li, Wei Wei, Qingyi 2020-12-01T14:26:54Z 2020-12-01T14:26:54Z 2020-11-16
dc.identifier.issn 2045-7634
dc.identifier.issn 2045-7634
dc.description.abstract Because the cadherin-mediated signaling pathway promotes cancer progression, we assessed associations between genetic variants in 109 cadherin-related genes and risk of pancreatic cancer (PanC) by using genotyping data from publically available genome-wide association studies (GWAS) datasets comprising 15,423 individuals of European ancestry. After initial single-locus analyses and subsequent meta-analysis with multiple testing correction for 29,963 single-nucleotide polymorphisms (SNPs), 11 SNPs remained statistically significant (p < 0.05). In the stepwise logistic regression analysis, three independent PanC risk-associated SNPs (KIF5B rs211304 C > G, FMN1 rs117648907 C > T, and MGAT3 rs34943118 T > C) remained statistically significant (p < 0.05), with odds ratios of 0.89 (95% confidence interval = 0.82-0.95 and p = 6.93 × 10-4 ), 1.33 (1.13-1.56 and 2.11 × 10-4 ), and 1.11 (1.05-1.17 and 8.10 × 10-5 ), respectively. Combined analysis of unfavorable genotypes of these three independent SNPs showed an upward trend in the genotype-risk association (ptrend  < 0.001). Expression quantitative trait loci analyses indicated that the rs211304 G and rs34943118 C alleles were associated with increased mRNA expression levels of KIF5B and MGAT3, respectively (all p < 0.05). Additional bioinformatics prediction suggested that these three SNPs may affect enhancer histone marks that likely have an epigenetic effect on the genes. Our findings provide biological clues for these PanC risk-associated SNPs in cadherin-related genes in European ancestry populations, possibly by regulating the expression of the affected genes. However, our findings need to be validated in additional population, molecular and mechanistic investigations.
dc.language eng
dc.publisher Wiley
dc.relation.ispartof Cancer medicine
dc.relation.isversionof 10.1002/cam4.3603
dc.subject cadherin pathway
dc.subject pancreatic cancer
dc.subject risk analysis
dc.subject single-nucleotide polymorphism
dc.title Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk.
dc.type Journal article Luo, Sheng|0796693 Moorman, Patricia G|0118714 Walsh, Kyle M|0429230 Wei, Qingyi|0632334 2020-12-01T14:26:50Z
pubs.organisational-group School of Medicine
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Population Health Sciences
pubs.organisational-group Pathology
pubs.organisational-group Neurosurgery
pubs.organisational-group Duke
pubs.organisational-group Institutes and Centers
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke Global Health Institute
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group University Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Biostatistics & Bioinformatics
pubs.publication-status Published
duke.contributor.orcid Luo, Sheng|0000-0003-4214-5809
duke.contributor.orcid Moorman, Patricia G|0000-0002-2978-6495
duke.contributor.orcid Walsh, Kyle M|0000-0002-5879-9981
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439

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