Yashiro Masakazu
Department of Surgical Oncology, Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan,
Dig Dis Sci. 2015 Aug;60(8):2251-63. doi: 10.1007/s10620-015-3646-4. Epub 2015 Apr 4.
Inflammatory bowel disease (IBD) is an important etiologic factor in the development of colorectal cancer (CRC). The risk of CRC begins to increase 8 or 10 years after the diagnosis of IBD. This type of cancer is called colitis-associated CRC (CA-CRC). The molecular pathogenesis of inflammatory epithelium might play a critical role in the development of CA-CRC. Genetic alterations detected in CA-CRC such as genetic mutations, microsatellite instability, and DNA hypermethylation are also recognized in sporadic CRC; however, there are differences in the timing and frequency of molecular events between CA-CRC and sporadic CRC. Interaction between gene-environmental factors, including inflammation, lifestyle, psychological stress, and prior appendectomy, might be associated with the etiopathology of IBD. The mucosal inflammatory mediators, such as oxidant stress, free radicals, and chemokines, may cause the genetic alterations. Understanding the molecular mechanisms of CA-CRC might be important to develop clinical efficacies for patients with IBD. This review discusses the molecular characteristics of CA-CRC, especially ulcerative colitis-associated CRC, including clinical features, signaling pathways, and interactions between genetic alterations and environment involved in inflammatory carcinogenesis.
炎症性肠病（IBD）是结直肠癌（CRC）发生发展的一个重要病因。CRC的风险在IBD诊断后8或10年开始增加。这种类型的癌症称为结肠炎相关结直肠癌（CA-CRC）。炎症上皮的分子发病机制可能在CA-CRC的发生发展中起关键作用。在CA-CRC中检测到的基因改变，如基因突变、微卫星不稳定性和DNA高甲基化，在散发性CRC中也有发现；然而，CA-CRC和散发性CRC在分子事件的发生时间和频率上存在差异。基因-环境因素之间的相互作用，包括炎症、生活方式、心理压力和既往阑尾切除术，可能与IBD的病因病理相关。黏膜炎症介质，如氧化应激、自由基和趋化因子，可能导致基因改变。了解CA-CRC的分子机制对于开发针对IBD患者的临床疗效可能很重要。本综述讨论了CA-CRC的分子特征，特别是溃疡性结肠炎相关结直肠癌，包括临床特征、信号通路以及炎症致癌过程中基因改变与环境之间的相互作用。
