Review article: the chemoprevention of colorectal carcinoma.
This review aims to provide an insight into some of the common pathways involved in the development of colorectal cancer--so-called chromosomal instability and microsatellite instability. There is both clinical and molecular evidence to show that colorectal cancer development occurs over an extended period of time. Together with a knowledge of the molecular pathogenesis of colorectal cancer, this time window allows physicians to counteract cancer development, a strategy known as chemoprevention. In familial and sporadic colorectal cancer, aspirin, other nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors have been tested for their ability to reduce polyp and cancer development in clinical studies. In inflammatory bowel disease-related colorectal cancer, evidence from retrospective case-control studies shows that mesalazine (mesalamine) can reduce the development of dysplastic lesions or cancer. Although the mechanisms behind this are incompletely understood, general anti-inflammatory, oxygen scavenger and some pro-apoptotic and cyclo-oxygenase inhibitory activities of mesalazine are thought to be involved. New molecular evidence points to a direct DNA stabilizing effect of mesalazine, resulting in a significant reduction of spontaneous microsatellite mutations.
Gasche
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Department of Internal Medicine IV, Division of Gastroenterology and Hepatology, Vienna, Austria. christoph.gasche@meduniwien.ac.at
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects; D018890:Chemoprevention; D043171:Chromosomal Instability / Q000235:genetics; D003092:Colitis / Q000150:complications; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D019804:Mesalamine / Q000009:adverse effects; D018895:Microsatellite Repeats; D011230:Precancerous Conditions
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D019804:Mesalamine; D001241:Aspirin