Risques Rosa Ana, Rabinovitch Peter S, Brentnall Teresa A
Department of Pathology, University of Washington, USA.
Curr Opin Gastroenterol. 2006 Jul;22(4):382-90. doi: 10.1097/01.mog.0000231812.95525.a7.
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.
患有慢性炎症性肠病（如溃疡性结肠炎和克罗恩病）的患者患结直肠癌的风险增加。需要进行终身结肠镜监测以检测发育异常的存在，但这种方法昂贵且耗时。因此，人们正在深入研究以确定具有预后价值的分子因素。本综述总结了近期的研究，特别强调了这些分子改变背后的机制。
染色体不稳定在炎症性肠病相关结直肠癌进展中的作用是明确的，可能与损伤、炎症、修复和端粒缩短的慢性循环有关。微卫星不稳定的作用一直是讨论的主题，数据表明炎症性肠病中的微卫星不稳定可能与散发性结直肠癌中的微卫星不稳定不同。甲基化作为一种基因沉默机制，也在溃疡性结肠炎的肿瘤发生中起作用。慢性炎症与p53激活和氧化应激有关，导致在溃疡性结肠炎中观察到广泛的基因组DNA损伤。
对炎症性肠病中癌症进展分子生物学的更好理解有望导致识别有用的预后生物标志物。现在需要努力证明目前已确定的最有前景标志物的临床实用性。
