胃癌是常见的恶性肿瘤，存在个体易感性，但其病因和机制尚不很清楚。申请者前期发现，PI3K/Akt/mTOR通路关键基因遗传变异参与胃癌发生发展。研究表明，非编码RNA（ncRNA）及其遗传变异可调控PI3K/Akt/mTOR通路参与肿瘤发生发展，但尚未见与胃癌的相关报道。本研究拟采用高通量检测、系统生物信息学分析、多阶段人群验证，筛选靶向调控PI3K/AKT/mTOR通路的ncRNAs；运用分子流行病学方法，在多阶段人群中评价ncRNAs基因的单核苷酸多态性（SNP）与胃癌发病风险的关联性强度及其可能的交互作用；采用双荧光素酶报告基因、基因编辑、染色体构象捕获、裸鼠荷瘤等实验，探讨易感位点及其宿主ncRNAs调控PI3K/AKT/mTOR通路参与胃癌发生发展的遗传和表观遗传调控机制。该研究将进一步揭示胃癌发病机理，为今后实施胃癌的个体化预防、干预和治疗等提供理论依据和重要参考。

Gastric cancer is a common malignant tumor existing individual susceptibility, but its etiology and mechanism is not very clear. We have found that the genetic variation of key genes from PI3K/Akt/mTOR pathway was involved in the development of gastric cancer. Studies have shown that noncoding RNA (ncRNA) and its genetic variation can regulate PI3K/Akt/mTOR pathway involved in the development of tumor, but it has not yet been reported in gastric cancer. In this study, ncRNAs targeting PI3K/AKT/mTOR pathway will be screened by high-throughput detection, systematic bioinformatics analysis and multi-stage population validation. The molecular epidemiology methods are used to evaluate the relationship between single nucleotide polymorphism (SNP) of ncRNAs gene and gastric cancer risk and its possible interaction in multi-stage population. The methods of double luciferase reporter gene, gene editing, chromosome conformation capture and nude mice bearing tumor will be used to explore the genetic and epigenetic mechanisms of risk SNPs and its host ncRNAs by regulating PI3K/AKT/mTOR pathway in the development and progression of gastric cancer. The study will further reveal the pathogenesis of gastric cancer, and provide theoretical basis and important reference for the future implementation of individual prevention, intervention and treatment on gastric cancer.