Nakanishi Risa, Shimizu Takahiro, Kumagai Ken, Takai Atsushi, Marusawa Hiroyuki
Department of Gastroenterology, Red Cross Osaka Hospital, Osaka 543-8555, Japan.
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Pathogens. 2021 Apr 9;10(4):453. doi: 10.3390/pathogens10040453.
Epidemiological, clinical, and biological studies convincingly demonstrate that chronic inflammation predisposes to the development of human cancers. In digestive organs, inflammation-associated cancers include colitis-associated colorectal cancers, -associated gastric cancer, as well as Barrett's esophagus and esophageal adenocarcinoma associated with chronic duodenogastric-esophageal reflux. Cancer is a genomic disease, and stepwise accumulation of genetic and epigenetic alterations of tumor-related genes leads to the development of tumor cells. Recent genome analyses show that genetic alterations, which are evoked by inflammation, are latently accumulated in inflamed epithelial cells of digestive organs. Production of reactive oxygen and aberrant expression of activation-induced cytidine deaminase, a nucleotide-editing enzyme, could be induced in inflamed gastrointestinal epithelial cells and play a role as a genomic modulator of inflammation-associated carcinogenesis. Understanding the molecular linkage between inflammation and genetic alterations will open up a new field of tumor biology and provide a novel strategy for the prevention of inflammation-associated tumorigenesis.
流行病学、临床和生物学研究有力地证明，慢性炎症易引发人类癌症。在消化器官中，炎症相关癌症包括结肠炎相关的结直肠癌、胃炎相关的胃癌，以及与慢性十二指肠胃食管反流相关的巴雷特食管和食管腺癌。癌症是一种基因组疾病，肿瘤相关基因的遗传和表观遗传改变逐步积累导致肿瘤细胞的发生。最近的基因组分析表明，由炎症引发的遗传改变潜伏地积累在消化器官的炎症上皮细胞中。炎症性胃肠上皮细胞中可诱导产生活性氧和活化诱导胞苷脱氨酶（一种核苷酸编辑酶）的异常表达，它们在炎症相关致癌作用中作为基因组调节剂发挥作用。了解炎症与遗传改变之间的分子联系将开辟肿瘤生物学的新领域，并为预防炎症相关肿瘤发生提供新策略。
