癌变
结直肠癌
溃疡性结肠炎
医学
炎症性肠病
发育不良
微卫星不稳定性
癌症
结肠炎
炎症
大肠癌小鼠模型的建立
DNA错配修复
免疫学
基因组不稳定性
内科学
DNA修复
癌症研究
生物
DNA损伤
疾病
病理
基因
遗传学
DNA
等位基因
微卫星
作者
Thomas Ullman,Steven H. Itzkowitz
出处
期刊:Gastroenterology
[Elsevier]
日期:2011-05-01
卷期号:140 (6): 1807-1816.e1
被引量:900
标识
DOI:10.1053/j.gastro.2011.01.057
摘要
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.
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