Year-end Sale % OFF 
Abstract
BackgroundPancreatic cancer is the fourth leading cause of cancer death in the U.S. and the etiology of this highly lethal disease has not been well defined. To identify genetic susceptibility factors for pancreatic cancer, we conducted pathway analysis of genome-wide association study (GWAS) data in 3,141 pancreatic cancer patients and 3,367 controls with European ancestry.MethodsUsing the gene set ridge regression in association studies (GRASS) method, we analyzed 197 pathways identified from the Kyoto Encyclopedia of Genes and Genomes database. We used the logistic kernel machine (LKM) test to identify major contributing genes to each pathway. We conducted functional enrichment analysis of the most significant genes (P<0.01) using the Database for Annotation, Visualization, and Integrated Discovery (DAVID).ResultsTwo pathways were significantly associated with risk of pancreatic cancer after adjusting for multiple comparisons (P<0.00025) and in replication testing: neuroactive ligand-receptor interaction, (Ps<0.00002), and the olfactory transduction pathway (P = 0.0001). LKM test identified four genes that were significantly associated with risk of pancreatic cancer after Bonferroni correction (P<1×10−5): ABO, HNF1A, OR13C4, and SHH. Functional enrichment analysis using DAVID consistently found the G protein-coupled receptor signaling pathway (including both neuroactive ligand-receptor interaction and olfactory transduction pathways) to be the most significant pathway for pancreatic cancer risk in this study population.ConclusionThese novel findings provide new perspectives on genetic susceptibility to and molecular mechanisms of pancreatic cancer.
Highlights
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, accounting for more than 37,660 deaths per year [1]
Three pathways were significant at P values,0.0001: neuroactive ligand-receptor interaction, longterm depression, and maturity onset diabetes of the young (MODY) pathways
To investigate if the significance of the olfactory transduction pathway (353 genes and 1,122 eigenSNPs) and the neuroactive ligand receptor interaction pathway (263 genes and 1,374 eigenSNPs) was due to their large size, we tested these pathways by applying the gene set ridge regression in association studies (GRASS) to the Wellcome Trust Case Control Consortium (WTCCC) genome-wide association study (GWAS) data and obtained a P value of 0.5652 and 0.2332 for bipolar disorder and 0.246 and 0.0062 for Crohn’s disease, respectively
Summary
Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, accounting for more than 37,660 deaths per year [1]. A recent study analyzed the GWAS data focusing on 23 selected pathways or groups of genes and identified the pancreas development pathway genes as susceptibility factors for pancreatic cancer [13]. While this data supports the candidate pathway analysis as a useful approach in genetic association study, it is limited by the number of pathways/genes examined, suggesting that a more comprehensive agnostic analysis of all known pathways may have the potential to uncover novel genes that were previously not considered in pancreatic cancer. To identify genetic susceptibility factors for pancreatic cancer, we conducted pathway analysis of genome-wide association study (GWAS) data in 3,141 pancreatic cancer patients and 3,367 controls with European ancestry
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
