Pathogenesis of Helicobacter pylori in the gastric carcinoma: A narrative reviews

Abstract

Helicobacter pylori is a gram-negative, flagellate, microaerophilic bacterium classified by international organizations as a biological class I carcinogenic agent. It is the recognized by international institutions for cancer research as a causative agent of infection-mediated carcinogenesis and is the most prevalent among infection-mediated cancers worldwide. This review aims to describe how Helicobacter pylori causes gastric cancer through its bacterial structures and/or secretory products. This narrative review summarizes current knowledge on H. pylori -induced gastric carcinogenesis using a non-systematic search of studies (1990–2024). Key literature on bacterial virulence, host responses, molecular mechanisms, and epithelial transformation was critically reviewed to highlight the pathogenic pathways linking chronic infection to gastric cancer. It induces gastric cancer by transforming gastric epithelial cells into an immortal state through different mechanisms. Complex combinations of host epigenetic and bacterial virulence factors determine the susceptibility and severity of the outcome in a subset of individuals. Gastric carcinogenesis is mostly dependent on strain variants of Helicobacter pylori which possess virulence factors for the pathogenesis and mediation of inflammation. Among the most studied virulence factors of Helicobacter pylori , cytotoxicity-associated gene A protein, vacuolation cytotoxic protein A, and some outer membrane proteins are rate-limiting factors for bacterial effects on gastric carcinoma development. To date, substantial advancements have been made in the comprehensive understanding of Helicobacter pylori pathogenesis, its complex biological effects, and its role in gastric mucosal carcinogenesis. Progress in molecular biology, immunopathology, and microbial genomics has elucidated key mechanisms by which the bacterium promotes epithelial transformation and tumor progression. Concurrently, significant improvements in diagnostic technologies have enhanced the early detection of both H. pylori infection and precancerous mucosal alterations, facilitating timely clinical intervention and risk stratification. However, more research is needed to fully understand the roles of other H. pylori gene products in cancer development. • H. pylori infects 50% globally, raising gastric cancer risk significantly. • CagA and VacA disrupt cells, causing inflammation and DNA damage. • H. pylori causes chronic inflammation, fostering a cancer-prone environment. • H. pylori disrupts gastric microbiota, reducing its composition and diversity. • Biomarker research aims to improve early H. pylori- related cancer diagnosis.