Integrated Cancer Prevention Center, Tel Aviv Souraski Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel.
Curr Opin Pharmacol. 2009 Aug;9(4):405-10. doi: 10.1016/j.coph.2009.06.006. Epub 2009 Jul 7.
Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). However, the underlying mechanisms are not entirely clear. A genetic basis for the increased risk of CRC in IBD patients is only a partial explanation. It is possible that high levels of inflammatory mediators that are produced in this setting may contribute to the development and progression of CRC. Growing evidence supports a role for various cytokines, released by epithelial and immune cells, in the pathogenesis of IBD-associated neoplasia. Two key genes in the inflammatory process, cyclooxygenase-2 (COX-2) and nuclear factor kappaB (NF-kappaB), provide a mechanistic link between inflammation and cancer while other factors such as, TNF-alpha and IL-6-induced signaling have been recently shown to promote tumor growth in experimental models of colitis-associated cancer. This article reviews the pathogenesis of IBD-related CRC and summarizes the molecular mechanisms underlying the development of intestinal neoplasia in the setting of chronic inflammation.
患有长期炎症性肠病（IBD）的患者患结直肠癌（CRC）的风险增加。然而，其潜在机制尚不完全清楚。IBD 患者 CRC 风险增加的遗传基础只是部分解释。在这种情况下产生的高水平炎症介质可能有助于 CRC 的发展和进展。越来越多的证据支持各种细胞因子在炎症过程中释放，由上皮细胞和免疫细胞释放，在炎症性肠病相关肿瘤发生的发病机制中发挥作用。炎症过程中的两个关键基因，环氧化酶-2（COX-2）和核因子 kappaB（NF-kappaB），为炎症和癌症之间提供了一个机制联系，而其他因素，如 TNF-α和 IL-6 诱导的信号转导，最近已被证明可促进结肠炎相关癌症实验模型中的肿瘤生长。本文综述了 IBD 相关 CRC 的发病机制，并总结了慢性炎症背景下肠道肿瘤发生的分子机制。
