title: Intestinal inflammation and cancer.
abstract: Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer (CRC). Chronic inflammation is believed to promote carcinogenesis. The risk for colon cancer increases with the duration and anatomic extent of colitis and presence of other inflammatory disorders (such as primary sclerosing cholangitis), whereas it decreases when patients take drugs to reduce inflammation (such as mesalamine and steroids). The genetic features that lead to sporadic CRC-chromosome instability, microsatellite instability, and DNA hypermethylation-also occur in colitis-associated CRC. Unlike the normal colonic mucosa, cells of the inflamed colonic mucosa have these genetic alterations before there is any histologic evidence of dysplasia or cancer. The reasons for these differences are not known, but oxidative stress is likely to be involved. Reactive oxygen and nitrogen species produced by inflammatory cells can affect regulation of genes that encode factors that prevent carcinogenesis (such as p53, DNA mismatch repair proteins, and DNA base excision-repair proteins), transcription factors (such as nuclear factor-κB), or signaling proteins (such as cyclooxygenases). Administration of agents that cause colitis in healthy rodents or genetically engineered, cancer-prone mice accelerates development of colorectal tumors. Mice genetically prone to inflammatory bowel disease also develop CRC, especially in the presence of bacterial colonization. Individual components of the innate and adaptive immune response have also been implicated in carcinogenesis. These observations offer compelling support for the role of inflammation in colon carcinogenesis.
authors.affiliation: The Dr Henry D. Janowitz Division of Gastroenterology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Ullman
authors.forename: Steven H
authors.initials: SH
authors.lastname: Itzkowitz
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000150:complications; D003093:Colitis, Ulcerative / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D003424:Crohn Disease / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D018384:Oxidative Stress; D012307:Risk Factors
chemical_list: D000893:Anti-Inflammatory Agents