幽门螺杆菌感染是胃癌最主要的环境病因，宿主遗传变异是胃癌易感性的基础，阐明二者的交互作用将促进胃癌的精准防治。既往研究提示已知胃癌易感区域5p13.1可能与幽门螺杆菌感染存在交互作用，本项目前期的实验发现，该区域的遗传变异可应答幽门螺杆菌感染激活的NF-κB信号，同时其基因型与PTGER4表达水平显著相关；然而，该区域遗传变异与幽门螺杆菌感染在胃癌发生中的交互作用机制有待深入阐明。因此，本项目拟首先采用巢式病例对照研究设计，评估5p13.1区域遗传变异与幽门螺杆菌感染的交互作用及其强度；进而通过生物信息学分析和生物功能学实验研究两者调控PTGER4的交互作用机制；最后在分子和细胞水平探究PTGER4在胃癌发生中的生物学作用。本项目的实施有助于揭示宿主遗传变异与幽门螺杆菌感染在胃癌发生中的交互作用机理，将为阐明胃癌发生机制提供新视角，同时也为胃癌预防提供理论基础和技术支撑。

Helicobacter pylori (H. pylori) infection is the most important environmental factor of gastric cancer, while host genetic variants determine the susceptibility to gastric cancer. Integrating genetic and environmental factors and understanding their interaction will promote accurate prevention and treatment of gastric cancer. Previous studies have confirmed that genetic variation at 5p13.1 interacted with H. pylori infection in gastric cancer development. Our preliminary analysis suggested that the functional genetic variation rs59133000 at 5p13.1 can respond to the NF-κB signal activated by H. pylori infection, and regulate the expression of PTGER4. However, the specific interaction and mechanism still need to be comprehensively clarified. Therefore, in this project, we will first perform a nested case-control study design to assess whether there is an interaction between rs59133000 and H. pylori infection in Chinese population. And further explore the biological mechanisms of interacted functional variant and H. pylori infection in regulating PTGER4 in gastric cancer through the bioinformatics analysis and functional experiment. In addition, we will explore the mechanism of PTGER4 promoting gastric cancer development at the molecular and cellular level. In summary, the implementation of this project will help to reveal the interaction mechanism between host genetic variation and H. pylori infection in the development of gastric cancer. It also not only provide a new perspective for elucidating the mechanism of gastric cancer, but also provide new theoretical foundations and technical support for gastric cancer prevention.