Study of Helicobacter pylori Isolated from a High-Gastric-Cancer-Risk Population: Unveiling the Comprehensive Analysis of Virulence-Associated Genes including Secretion Systems, and Genome-Wide Association Study

SIMPLE SUMMARY: Helicobacter pylori infection is known to be a major risk factor for gastric cancer, which continues to be a huge health burden worldwide, especially in Mongolia. There is a complicated interaction between host genetics, environmental factors, and bacterial virulence determinants in the etiology of this cancer. The virulence factors produced by this bacterium are among the most important contributors to the onset of gastric cancer. This study provides an accessible introduction to the relationship between H. pylori infection and gastric cancer and focuses on elucidating the impact of H. pylori’s varying virulence factors on a set of virulence-associated genes at the level of gene presence or absence and single nucleotide polymorphisms from a genome-wide H. pylori perspective on gastric disease progression. Current results provide the basis for gastric progression depending on bacterial factors and help to find new insights into the prevention and treatment of gastric cancer. ABSTRACT: Background: The prevalence of gastric cancer in Mongolia, in East Asia, remains the highest in the world. However, most Helicobacter pylori strains in Mongolia have a less virulent Western-type CagA. We aimed to determine how H. pylori genomic variation affected gastric diseases, especially gastric cancer, based on comprehensive genome analysis. Methods: We identified a set of 274 virulence-associated genes in H. 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 223 H. pylori strains and their associations with gastric cancer and other gastric diseases. We conducted a genome-wide association study on 158 H. pylori strains (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. pylori strains 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 virulent H. pylori strains may adapt through host-influenced genomic variations, potentially impacting gastric carcinogenesis.