微卫星不稳定性
炎症性肠病
溃疡性结肠炎
结直肠癌
疾病
医学
癌症
癌变
发育不良
基因组不稳定性
生物信息学
免疫学
作者
Rosa Ana Risques,Peter S. Rabinovitch,Teresa A. Brentnall
出处
期刊:Current Opinion in Gastroenterology
[Ovid Technologies (Wolters Kluwer)]
日期:2006-07-01
被引量:43
标识
DOI:10.1097/01.mog.0000231812.95525.a7
摘要
Patients with chronic inflammatory bowel disease, such as ulcerative colitis and Crohn's disease, have an increased risk of colorectal cancer. Life-long colonoscopy surveillance is performed to detect the presence of dysplasia, but this approach is expensive and time-consuming. Thus, there is intensive research to identify molecular factors with prognostic value. This review summarizes recent research, with a special emphasis on the mechanisms underlying these molecular alterations.The role of chromosomal instability in the progression to inflammatory bowel disease-associated colorectal cancer is clear and likely relates to chronic cycles of injury, inflammation, repair and telomere shortening. The role of microsatellite instability has been a subject of discussion, and data suggest that microsatellite instability in inflammatory bowel disease might be different from microsatellite instability in sporadic colorectal cancer. Methylation, as a mechanism of gene silencing, also plays a role in ulcerative colitis tumorigenesis. Chronic inflammation has been linked to p53 activation and oxidative stress, contributing to the extensive genomic DNA damage observed in ulcerative colitis.Improved understanding of the molecular biology of cancer progression in inflammatory bowel disease will hopefully lead to the identification of useful prognostic biomarkers. Efforts are needed to prove the clinical utility of the most promising markers now identified.
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