Background: The prevalence of gastric cancer in Mongolia, in East Asia, remains the highest in the world. However, mostHelicobacter pyloristrains in Mongolia have a less virulent Western-type CagA. We aimed to determine howH. pylorigenomic variation affected gastric diseases, especially gastric cancer, based on comprehensive genome analysis. Methods: We identified a set of 274 virulence-associated genes inH. pylori, including virulence factor and outer membrane protein (OMP) genes, the type four secretion system gene cluster, and 13 well-known virulence gene genotypes in 223H. pyloristrains and their associations with gastric cancer and other gastric diseases. We conducted a genome-wide association study on 158H. pyloristrains (15 gastric cancer and 143 non-gastric cancer strains). Results: Out of 274 genes, we found 13 genes were variable depending on disease outcome, especially iron regulating OMP genes.H. pyloristrains from Mongolia were divided into two main subgroups: subgroup (Sg1) with high risk and Sg2 with low risk for gastric cancer. The general characteristics of Sg1 strains are that they possess more virulence genotype genes. We found nine non-synonymous single nucleotide polymorphisms in seven genes that are linked with gastric cancer strains. Conclusions: Highly virulentH. pyloristrains may adapt through host-influenced genomic variations, potentially impacting gastric carcinogenesis.
背景：蒙古作为东亚地区，其胃癌患病率仍居世界首位。然而，蒙古境内大多数幽门螺杆菌菌株携带的CagA毒力因子属于毒力较弱的西方型。本研究旨在通过全基因组分析，探究幽门螺杆菌基因组变异如何影响胃部疾病，特别是胃癌的发生。方法：我们在223株幽门螺杆菌菌株中鉴定出274个毒力相关基因，包括毒力因子基因、外膜蛋白基因、IV型分泌系统基因簇以及13种已知毒力基因型，并分析其与胃癌及其他胃部疾病的关联。对158株幽门螺杆菌菌株（15株胃癌相关菌株和143株非胃癌相关菌株）进行了全基因组关联分析。结果：在274个基因中，我们发现13个基因的表达随疾病结局呈现显著差异，其中铁调节外膜蛋白基因尤为突出。蒙古的幽门螺杆菌菌株可分为两个主要亚群：胃癌高风险亚群（Sg1）和低风险亚群（Sg2）。Sg1菌株的普遍特征为携带更多毒力基因型。我们在7个基因中发现了9个与胃癌菌株相关的非同义单核苷酸多态性。结论：高毒力幽门螺杆菌菌株可能通过宿主影响的基因组变异实现适应性进化，这一过程可能对胃癌发生发展产生影响。
肿瘤(癌症)患者之家