Helicobacter pylori (H. pylori), a bacterial carcinogen, is the most important risk factor for gastric cancer. Globally, about 75% of gastric cancers and 5.5% of malignancies are associated with H. pylori-induced inflammation and injury, however, the mechanism of H. pylori carcinogenesis has not been fully elucidated. Gastroenterology. The interaction between microbial and human genetic origins H. pylori strains are genetically polymorphic and can freely recombine with human host genes in the same region Linz et al. found through multilocus sequence typing that H. pylori strains can isolate multiple geographically related strains from their hosts. The relationship between H. pylori and humans has evolved over more than 100,000 years, reaching a durable mutual adaptation and a gradual decrease in virulence over time. However, once this coevolutionary state is broken, it will initiate pathophysiological processes that cause disease and become the greatest risk factor for gastric cancer. In some regions, the incidence of gastric cancer coincides with the incidence of H. pylori infection (e.g. Asia), however, in some regions the incidence of gastric cancer is low despite the high prevalence of H. pylori infection (e.g. Africa). correa et al. reported an overall prevalence of >90% in the Colombian region and an incidence of gastric cancer of 150 per 100,000 inhabitants in mountainous areas, while the incidence in coastal areas was only 6 per 100,000. These differences provide an opportunity to evaluate the interaction of H. pylori in gastric carcinogenesis with human ancestry. Certainly, the risk of gastric mucosal atrophy developing into gastric cancer is lower than that of intestinal metaplasia or atypical hyperplasia, i.e., a state of equilibrium exists between certain H. pylori strains and their corresponding hosts, which is disrupted when the strain infects a host that does not match its genotype and pathogenicity begins to emerge. There is evidence that reciprocal host-pathogen genotype reactions can alter the risk of developing gastric cancer. On the bacterial side, strains with a major virulence factor, Cag virulence island, have a higher risk of carcinogenesis, and on the host side, polymorphisms of specific genes encoding inflammatory factors can increase the risk of gastric cancer in people infected with H. pylori. In addition, a study by Figueiiredo et al. concluded that hosts with high-risk factor genotypes infected with strains having the vacA allele or carrying the cag gene could significantly increase the risk of gastric cancer by approximately 87-fold. The virulence factor of H. pylori H. pylori has evolved to survive for a long time in the hostile environment of the human stomach and can adapt to the acidic environment and colonize the epithelial cell surface of the gastric mucosa through mobility, drug repellency, production of urease, and its metabolites can modulate the activity of epithelial cells and the inflammatory response. Schreiber et al. showed that most bacteria can move freely within the mucosal layer (below 25um from the gastric surface), which facilitates the approach of H. pylori bacteria to the epithelial cells and modulates the mucosal immune system, and that the metabolites of H. pylori, CagA and VacA (vacuolar toxin), can increase the risk of gastric cancer and gastric ulcers through these effects. In addition, VacA and CagA can interact when present together, e.g., Argent suggested that VacA can reduce the half-life of CagA by stimulating its degradation through the endocytosis pathway. It has been found that the half-life of CagA is increased in CD44+ stem cells with tumorigenic properties and is not affected by VacA. Thus, CagA is more pathogenic in precursor cells, transformed cells, and stem cells. H.pylori and gastric stem cells H.pylori colonizes the mucus surface of the gastric mucosa and adheres to crypt cells in the mucosa. The above terminally differentiated cells may be the target cells for H.pylori to cause oncogenic transformation of cells that can transform into proliferating cells and acquire oncogenic mutations as well as cancer stem cell characteristics by dedifferentiation. However, surface mucous cells have a short survival period (1-2 days) and therefore have a limited response to H.pylori or inflammatory factors. h.pylori causes hyperplasia or a severe inflammatory response in chronic active gastritis by expanding the area of cell proliferation in the upper part of the gland, which may lead to contact of immature cells with bacteria. Chronic atrophic gastritis is mostly accompanied by proliferation of immature cells, and the interaction of H. pylori with progenitor cells, which internalize some of the bacteria, can be observed in a mouse model of atrophic gastritis. The results of this study suggest that adult gastric stem cells are a sheltered site for some H. pylori subtypes, sparing them from clearance by the body. In addition, local inflammatory responses may be associated with disease progression, such as infiltration of neutrophils in the proliferating regions of the gastric pits as a pathophysiological feature of H.pylori-induced gastritis. Interactions between H. pylori and proliferating progenitor cells may continue throughout the life course of the organism, and these interactions may also directly or indirectly cause malignancy. It has also been suggested that changes in the number or damage of stem cells are associated with the progression of gastric tumors, and that high levels of LGR5 may be an indicator of poor prognosis in gastric cancer patients. In addition to these effects, H. pylori may adhere directly to the epithelial cells of the gastric mucosa or even colonize the epithelial cell junctions in the gastric glands in order to avoid the action of gastric acid or the immune system.