New aspects of Helicobacter pylori infection involvement in gastric oncogenesis.
Gastric adenocarcinoma not located in the cardia still remains second only to lung cancer as the leading cause of cancer-related mortality worldwide, whereas adenocarcinoma of the cardia and gastroesophageal junction has been rapidly rising over the past two decades. Gastric malignancy can be subdivided into diffuse and intestinal pathologic entities that have different epidemiological and prognostic features. Various genetic and environmental factors lead to either abnormal gene overexpression or inappropriate expression of normal genes, whose products confer the malignant phenotype. Advances have been made in genetic changes mostly of the intestinal type; its development is probably a multistep process, as has been well described in colon carcinogenesis. Oncogene overexpression, tumor suppressor loss, and defective DNA mismatch repair is associated with gastric cancer. The most common genetic abnormalities tend to be loss of heterozygosity of particularly tumor suppressor p53 gene or "adenomatous polyposis coli" gene. The latter leads to gastric carcinogenesis through changes related to E-cadherin-catenin complex, which plays a critical role in normal tissue architecture maintenance. Mutation of any of its components results in loss of cell-cell adhesion, thereby contributing to malignancy. Putative trophic factors have also been involved in gastric oncogenesis. E-cadherin/CDH1 gene germline mutations have been recognized in families with an inherited predisposition to diffuse-type malignancy. This review focuses mainly on Helicobacter pylori infection involved in gastric carcinogenesis through various mechanisms, including repopulation of the stomach with bone marrow-derived stem cells that may facilitate gastric cancer progression, thereby necessitating eradication of this bacterium.
Kountouras
Jannis
J
Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece. jannis@med.auth.gr
Zavos
Christos
C
Chatzopoulos
Dimitrios
D
Katsinelos
Panagiotis
P
D000230:Adenocarcinoma / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D013234:Stem Cells / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000473:pathology