Update on molecular pathogenesis of Helicobacter pylori-induced gastric cancer

Helicobacter pylori (H. pylori) infection is one of the most prevalent bacterial infections affecting mankind. About half of the world's population is infected with it. It causes several upper gastrointestinal diseases, including gastric cancer (GC). It has been identified as a major risk factor for GC. GC is one of the most common cancers affecting humans and the third leading cause of cancer-related deaths worldwide. H. pylori infection causes an inflammatory response that progresses through a series of intermediary stages of precancerous lesions (gastritis, atrophy, intestinal metaplasia, and dysplasia) to the final development of GC. Among infected individuals, approximately 10% develop severe gastric lesions such as peptic ulcer disease, 1%-3% progress to GC, and 0.1% develop mucosa-associated lymphoid tissue followed by the development of lymphoma. The bacterium has many virulence factors, including cytotoxin-associated gene A, vacuolating cytotoxin A, and the different outer membrane proteins that cause cancer by different mechanisms. These virulence factors activate cell signaling pathways such as PI3-kinase/Akt, JAK/STAT, Ras, Raf, and ERK signaling that control cell proliferation. Uncontrolled proliferation can lead to cancer. In addition, the repair of DNA damage may also be impaired by H. pylori infection. Reduced DNA repair in combination with increased DNA damage can result in carcinogenic mutations. The accurate identification of pathogenetic pathways is imperative for the development of targeted diagnostic markers and personalized treatments. This scoping review aims to update the readers on the role of H. pylori in the development of GC. It will focus on the molecular mechanisms underpinning gastric carcinogenesis in H. pylori infection. It will highlight the interaction between bacterial virulence factors and host cellular pathways, providing insights into potential therapeutic targets and preventive strategies.