title: Helicobacter pylori infection and carcinogenesis of the stomach.
abstract: BACKGROUND
  Human stomach carcinogenesis occurs after a multi-step process of genetic and epigenetic alterations in oncogenes, tumor-suppressor genes, cell-adhesion molecules, telomere and telomerase activity as well as genetic instability at several microsatellite loci.
  
  
  CONCLUSIONS
  These sequential alterations found in gastric cancer differ between the two histological types, indicating that different genetic pathways exist for well-differentiated or intestinal-type and poorly differentiated or diffuse-type gastric cancers, even though both types of gastric cancer may arise from epithelial "stem cells", which express human telomerase reverse transcriptase (hTERT) protein and telomerase activity. Infection with Helicobacter pylori, 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 increased telomerase activity as well as hTERT overexpression. They may precede DNA replication error, DNA hypermethylation, CD44 abnormal transcript, and p53 mutations, all of which occur in at least 30% of intestinal metaplasias as early events of multi-step pathogenesis of well-differentiated type gastric cancer. Here, we propose a new concept for gastric preneoplasic lesion, "metaplastic dysplasia", based on our molecular observations.
authors.affiliation: First Department of Pathology, Hiroshima University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kuniyasu
authors.forename: W
authors.initials: W
authors.lastname: Yasui
authors.forename: H
authors.initials: H
authors.lastname: Yokozaki
authors.forename: E
authors.initials: E
authors.lastname: Tahara
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D016481:Helicobacter Infections / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000473:pathology