[Mechanisms of H. pylori infection-induced gastric carcinogenesis]

Many epidemiological studies have demonstrated a strong association between H. pylori (Helicobacter pylori) infection and human gastric cancer development. The precise mechanisms accounting for gastric cancer development induced by H. pylori infection are still not completely understood. However, it should be reasonable to assume that there are two distinct molecular pathways for gastric carcinogenesis by H. pylori infection; the direct action of the bacteria itself on gastric epithelial cells, and the accumulation of genetic changes caused by prolonged bacterial infection and chronic inflammation. As a direct action of H. pylori, bacterial proteins such as CagA could be delivered into gastric epithelial cells via the type IV secretion apparatus and modify the host cell functions related to cell proliferation. In addition to the direct bacterial action, H. pylori infection and the resultant inflammatory response cause various genetic and epigenetic changes in tumor-related genes of the gastric epithelial cells. Notably, expression of AID (activation-induced cytidine deaminase), a DNA editing enzyme that undergoes somatic hypermutation on human genes, is induced in response to H. pylori infection and proinflammatory cytokine stimulation in human gastric epithelial cells. As a result, the accumulation of genetic alterations would persist until the clinical stage of atrophic gastritis and eventually trigger the malignant transformation of gastric cells.