Pathogenicity of Helicobacter pylori-associated gastric cancer

Abstract

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide and ranks among the top five most common malignancies. Helicobacter pylori (H. pylori) infection is recognized as the primary risk factor, although gastric carcinogenesis also reflects complex interactions among bacterial virulence factors, host genetics, and the gastric microbiome. H. pylori harbors well-characterized proteins such as CagA, VacA, BabA, and SabA that enable persistent infection and fuel tumor initiation. Recent high-quality evidence from randomized trials and meta-analyses provide strong support that H. pylori eradication therapy substantially reduces cancer risk-even in those with established precancerous lesions such as intestinal metaplasia or dysplasia. Additionally, emerging research indicate that H. pylori may influence the tumor immune microenvironment, such as through altering programmed death ligand 1 expression-which could affect immunotherapy outcomes. This review presents a cohesive and updated perspective on H. pylori-driven GC, summarizing bacterial virulence, host predispositions, microbiome interactions, epigenetic changes like DNA repair gene methylation, and evolving therapeutic implications, all while illuminating current scientific debates and emerging directions.

Keywords: CagA; Gastric cancer; Helicobacter pylori; Microbiome; Virulence factors; cagPAI.

Figure 1

Multistep pathogenesis of Helicobacter pylori-induced gastric cancer. The diagram illustrates the progressive stages of Helicobacter pylori infection: From initial colonization and virulence factor expression (CagA and VacA) to activation of host immune responses (e.g., interleukin-8, tumor necrosis factor-alpha), chronic inflammation, tissue damage, atrophic gastritis, intestinal metaplasia, and eventual dysplasia leading to gastric cancer. IL: Interleukin; ROS: Reactive oxygen species; TNF-α: Tumor necrosis factor-alpha; H. pylori: Helicobacter pylori.