Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Cell Mol Gastroenterol Hepatol. 2021;11(4):1177-1197. doi: 10.1016/j.jcmgh.2020.12.013. Epub 2021 Jan 5.
Inflammatory bowel disease (IBD) patients have an increased risk of developing colitis-associated colon cancer (CAC); however, the basis for inflammation-induced genetic damage requisite for neoplasia is unclear. Several studies have shown that IBD patients have signs of increased oxidative damage, which could be a result of genetic and environmental factors such as an excess in oxidant molecules released during chronic inflammation, mitochondrial dysfunction, a failure in antioxidant capacity, or oxidant promoting diets. It has been suggested that chronic oxidative environment in the intestine leads to the DNA lesions that precipitate colon carcinogenesis in IBD patients. Indeed, several preclinical and clinical studies show that different endogenous and exogenous antioxidant molecules are effective at reducing oxidation in the intestine. However, most clinical studies have focused on the short-term effects of antioxidants in IBD patients but not in CAC. This review article examines the role of oxidative DNA damage as a possible precipitating event in CAC in the context of chronic intestinal inflammation and the potential role of exogenous antioxidants to prevent these cancers.
炎症性肠病(IBD)患者发生结肠炎相关性结肠癌(CAC)的风险增加;然而,炎症诱导的、发生肿瘤必需的遗传损伤的基础尚不清楚。一些研究表明,IBD 患者有氧化损伤增加的迹象,这可能是遗传和环境因素的结果,如慢性炎症期间释放的过多氧化剂分子、线粒体功能障碍、抗氧化能力的丧失,或促进氧化剂的饮食。有人认为,肠道内的慢性氧化环境会导致 DNA 损伤,从而引发 IBD 患者的结肠癌发生。事实上,一些临床前和临床研究表明,不同的内源性和外源性抗氧化分子在减少肠道氧化方面是有效的。然而,大多数临床研究都集中在抗氧化剂对 IBD 患者的短期作用,而不是 CAC。本文综述了氧化 DNA 损伤在慢性肠道炎症背景下作为 CAC 发生的一个可能的促成事件的作用,以及外源性抗氧化剂预防这些癌症的潜在作用。