Helicobactor pylori infection and carcinogenesis of the stomach

Introduction: Human stomach carcinogenesis occurs after a multi-step proces s of genetic and epigenetic alterations in oncogenes, tumor-suppressor gene s, cell-adhesion molecules, telomere and telomerase activity as well as gen etic instability at several microsatellite loci. Results and discussion: Th ese sequential alterations found in gastric cancer differ between the two h istological types, indicating that different genetic pathways exist for wel l-differentiated or intestinal-type and poorly differentiated or diffuse-ty pe gastric cancers, even though both types of gastric cancer may arise from epithelial "stem cells", which express human telomerase reverse transcript ase (hTERT) protein and telomerase activity. Infection with Helicobacter py lori, which evidently causes the release of reactive oxygen species (ROMs) and reactive nitrogen species (NO), may be a strong trigger for "stem cell" hyperplasia in intestinal metaplasia, followed by telomere reduction and i ncreased telomerase activity as well as hTERT overexpression. They may prec ede DNA replication error, DNA hypermethylation, CD44 abnormal transcript, and p53 mutations, all of which occur in at least 30% of intestinal metapla sias as early events of multi-step pathogenesis of well-differentiated type gastric cancer. Here, we propose a new concept for gastric preneoplasic le sion, "metaplastic dysplasia", based on our molecular observations.