Oncotarget

Research Papers:

SNP interactions of Helicobacter pylori-related host genes PGC, PTPN11, IL1B, and TLR4 in susceptibility to gastric carcinogenesis

Caiyun He, Huakang Tu, Liping Sun, Qian Xu, Yuehua Gong, Jingjing Jing, Nannan Dong and Yuan Yuan _

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Oncotarget. 2015; 6:19017-19026. https://doi.org/10.18632/oncotarget.4231

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Abstract

Caiyun He1,2, Huakang Tu3, Liping Sun1, Qian Xu1, Yuehua Gong1, Jingjing Jing1, Nannan Dong1 and Yuan Yuan1

1 Tumor Etiology and Screening Department of Cancer Institute and General Surgery, the First Affiliated Hospital of China Medical University, and Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, China

2 Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

3 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

Correspondence to:

Yuan Yuan, email:

Keywords: Helicobacter pylori, gastric cancer, atrophic gastritis, susceptibility, interaction

Received: March 24, 2015 Accepted: May 13, 2015 Published: May 22, 2015

Abstract

A series of host genes that respond to Helicobacter pylori (H. pylori) infection are involved in the process of gastric carcinogenesis. This study sought to examine interactions among polymorphisms of H. pylori-related genes PGC, PTPN11, TLR4, and IL1B and assess whether their interaction effects were modified by H. pylori infection. Thirteen polymorphisms of the aforementioned genes were genotyped by the Sequenom MassARRAY platform in 714 gastric cancer patients, 907 atrophic gastritis cases and 1276 healthy control subjects. When we considered the host genetic effects alone, gene–gene interactions consistently decreased the risks of gastric cancer and/or atrophic gastritis, including three two-way interactions: PGC rs6912200-PTPN11 rs12229892, PGC rs4711690-IL1B rs1143623 and PTPN11 rs12229892-IL1B rs1143623 and a three-way interaction: PGC rs4711690-PGC rs6912200-PTPN11 rs12229892. When the effect modification of H. pylori infection was evaluated, the cumulative effects of the aforementioned three-way interaction on atrophic gastritis susceptibility switched from being beneficial to being risky by the status of H. pylori infection. These data showed that SNP interactions among H. pylori-related genes PGC, PTPN11, and IL1B, are associated with susceptibility to gastric carcinogenesis. Moreover, we provided important hints of an effect modification by H. pylori infection on the cumulative effect of PGC and PTPN11 polymorphisms. Functional experiments and further independent large-scale studies especially in other ethnic populations are still needed to confirm our results.


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