title: New concepts of molecular biology for colon carcinogenesis.
abstract: The progressive accumulation of genetic changes in both oncogenes and tumor-suppressor genes parallels the clinical and histopathologic progression from normal colonic epithelium through benign adenomas to frank colon cancer. A similar progression is postulated in the transition of normal squamous epithelium to metaplastic mucosa (Barrett's esophagus) and subsequently through dysplasia to adenocarcinoma of the esophagus. A common link between colorectal cancer and Barrett's esophagus or esophageal carcinoma might be explained by either genetic predisposition or common environmental risk factors. The multistep nature of oncogenesis is most directly illustrated by molecular experimental genetic studies which demonstrate that the progression from adenoma to colon carcinoma results from the accumulation of molecular genetic alterations involving mainly 3 factors: activation of oncogenes; inactivation of tumor-suppressor genes; and abnormalities in genes involved in DNA mismatch repair. Changes in oncogenes encoding four distinct groups of proteins (peptide growth factors, protein kinases, signal transducing proteins, and nuclear transcriptional regulatory proteins) can contribute to colon carcinogenesis. In addition, various carcinogens may act at different stages of this model, affecting somatic mutations and resulting in additional genetic alterations. Other promoters, including hormones, may enhance the likelihood of these events through the stimulation of the rate of cell turnover. Diseased detoxification processes may also play a role in carcinogenesis.
authors: Department of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Greece. jannis@med.auth.gr
authors: J
authors: J
authors: Kountouras
authors: P
authors: P
authors: Boura
authors: N J
authors: NJ
authors: Lygidakis
mesh_terms: D015815:Cell Adhesion Molecules / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics*; D006801:Humans; D009857:Oncogenes / Q000235:genetics
chemical_list: D015815:Cell Adhesion Molecules