Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway and pancreatic cancer risk.
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.
Type
Journal articlePermalink
https://hdl.handle.net/10161/21772Published Version (Please cite this version)
10.1002/cam4.3603Publication Info
Zhao, Lingling; Liu, Hongliang; Luo, Sheng; Moorman, Patricia G; Walsh, Kyle M; Li,
Wei; & Wei, Qingyi (2020). Associations between genetic variants of KIF5B, FMN1, and MGAT3 in the cadherin pathway
and pancreatic cancer risk. Cancer medicine. 10.1002/cam4.3603. Retrieved from https://hdl.handle.net/10161/21772.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.
Collections
More Info
Show full item recordScholars@Duke
Sheng Luo
Professor of Biostatistics & Bioinformatics
Patricia Gripka Moorman
Professor Emeritus in Family Medicine and Community Health
Dr. Moorman's research focuses on the epidemiology of women's health issues. Her work
includes research on ovarian cancer, breast cancer and hysterectomy. Areas of particular
interest include disparities in cancer risk factors and outcomes and the effects of
hysterectomy on ovarian function. As part of the Duke Evidence Synthesis group, she
has also been involved in systematic reviews and meta-analyses related to ovarian
cancer, breast cancer and infertility.
Kyle Walsh
Associate Professor in Neurosurgery
Dr. Walsh is Associate Professor of Neurosurgery and Pathology, Director of the Division
of Neuro-epidemiology, and a Senior Fellow in the Duke Center for the Study of Aging
and Human Development. He leads Duke’s Neuro-epidemiology Lab, which integrates bench
science with statistical methods to study the neurobiology of glial senescence and
gliomagenesis. This research interrogates human genomic and epigenomic profiles to
identify both heritable and modifiable factors that contribute to ne
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
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info