New concepts of molecular biology on gastric carcinogenesis.
Gastric cancer not located in the cardia still remains the second most common cancer worldwide, whereas adenocarcinoma of the cardia and gastroesophageal junction has been rapidly rising over the past two decades. Gastric cancer can be subdivided into two distinct pathologic entities, diffuse and intestinal, that have different epidemiologic and prognostic features. Various genetic and environmental factors play important roles in gastric carcinogenesis; both lead to either abnormal genes overexpression or inappropriate expression of normal genes, whose products confer the malignant phenotype. Advances have been made in the genetic changes mostly of the intestinal type; its development is probably a multistep process, as has been well described in colon cancer pathogenesis, whereas it remains tentative whether the diffuse type of malignancy follows an analogous progression. The most common genetic abnormalities in gastric cancer tend to be loss of heterozygosity of tumor suppressor genes, particularly of p53 or "Adenomatous Polyposis Coli" gene. The latter leads to gastric oncogenesis through changes related to E-cadherin-catenin complex, which plays a critical role in the maintenance of normal tissue architecture. Mutation of any of its components results in loss of cell-cell adhesion, thereby contributing to neoplasia. E-cadherin/CDH1 gene germline mutations have been recognized in families with an inherited predisposition to gastric cancer of the diffuse type. Amplification and/or overexpression of putative trophic factors have also been observed in gastric cancer. Finally, Helicobacter pylori (H. pylori) infection is also involved in gastric carcinogenesis through various mechanisms, thereby necessitating H. pylori eradication in patients with gastric cancer.
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
D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*