Epstein-Barr Virus and <i>Helicobacter pylori</i> as Two Main Risk Factors in Gastric Cancer

Microbial and viral pathogens have emerged as key contributors to cancer development. Research conducted in the last twenty years has significantly enhanced our comprehension of the cancer-causing capabilities of infectious agents. An illustrative instance is gastric cancer (GC), which is closely associated with <em>Helicobacter pylori</em> (<em>H. pylori</em>) and Epstein-Barr virus (EBV) infections, with approximately 90% of non-cardia GC cases attributed to <em>H. pylori</em> infection and around 10% linked to EBV. Despite significant research efforts, GC remains a severe clinical challenge, ranking as the fifth most commonly diagnosed cancer worldwide. In 2020, an estimated 768,793 people died from GC in the world. The pathogenicity island (PAI), cagA protein, VacA, and other virulence factors in <em>H. pylori</em> and several latency factors such as EBNA-1, LMP-1, and LMP2A in Epstein-Barr virus, as well as pattern of gene methylation and EBV and <em>H. pylori</em> co-infection are shown as the leading causes of pathogen-related GC. The unique molecular and clinical characteristics associated with EBV and <em>H. pylori</em> in GC highlight the importance of further understanding their respective roles in GC development and progression. This knowledge may inform future preventive and therapeutic strategies targeting these infectious agents in the context of GC. This review aims to elucidate the mechanisms underpinning GC's EBV and H. pylori-induced carcinogenesis.