title: Review article: molecular basis of gastric carcinogenesis.
abstract: Gastric cancer is constituted by two histomorphological entities 'intestinal' and 'diffuse', however lesions with similar morphologies may differ in biological aggressiveness and response to therapy. Two distinct molecular pathways have been identified in gastric carcinogenesis: the microsatellite mutator phenotype and a phenotype associated with chromosomal and intrachromosomal instability. Mounting evidence suggests that microsatellite mutator phenotype alterations and expression of the products of cancer-related genes are early markers of cell transformation, and may serve to identify the gastric carcinoma histotypes. The lack of a clear genetic basis, lends weight to the notion that gastric cancer is not a monomorphic entity but may be affected by environmental factors. Helicobacter pylori is the most important environmental risk factor associated with sporadic gastric cancer. Exposure of gastric epithelial cells to bacterium results in the generation of reactive oxygen species and inducible nitric oxide synthase that in turn may cause genetic alterations leading to cancer in a subset of subjects. Thus, gastric cancer may be considered the result of an interplay between host genetic profile and environmental toxic agents. The new technologies of molecular analysis will help to establish an individual's risk of developing gastric cancer and will lead to novel biological therapeutic strategies.
authors.affiliation: Department of Clinical Medicine, Gastroenterologic Unit, University of Naples Federico II, Naples, Italy. nardone@unina.it
authors.forename: G
authors.initials: G
authors.lastname: Nardone
mesh_terms: D025063:Chromosome Disorders / Q000235:genetics; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics; D016480:Helicobacter pylori; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology