Cross-Disease Analysis Reveals Novel Risk Genes for Esophageal Adenocarcinoma

Background: Previous studies have shown that Helicobacter pylori infection (HPI) is related to a reduced risk of esophageal adenocarcinoma (EAC) by unknown biological mechanisms. It is hypothesized that EAC and HPI have strong genetic associations. Methods: An integrated analysis, using large-scale ResNet relation data and gene expression data for HPI and EAC, to identify potential EAC risk genes from a HPI-gene group was conducted. Diseasegene relation data were acquired from the Pathway Studio ResNet Mammalian database. Gene expression data were acquired from samples of 92 subjects including 64 EAC cases and 28 normal controls. Results: Genes linked to HPI and EAC present significant overlap (79 genes, p-value = 2.5E-75) and play roles within multiple common genetic pathways (enrichment p-value ≤ 5.05E-17 for the top 10 pathways) that are implicated with both diseases. A genetic network of 32 genes was identified through which HPI may exert influence on EAC. There were 6 HPI genes that presented significant differences (p-value < 1e-10) between EAC cases and controls, including: MUC13, AQP3, TFF3, SFTPD, NOD2, and PIGR. Network analysis showed that these genes demonstrated strong functional associations with EAC and may be potential EAC risk genes. Conclusion: Results from this study support the hypothesis that complex genetic associations exist between HPI and EAC, and that HPI-related genes may also play roles in EAC pathogenic http://mo.qingres.com Esophageal Adenocarcinoma Peng Zhou et al MED ONE 2016,1:e160022 | Email:[email protected] October 25, 2016 2 development. This provides new insights into EAC candidate gene identification.