Marusawa Hiroyuki
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Gan To Kagaku Ryoho. 2010 Jan;37(1):23-7.
Many epidemiological studies have demonstrated a strong association between H. pylori (Helicobacter pylori) infection and human gastric cancer development. The precise mechanisms accounting for gastric cancer development induced by H. pylori infection are still not completely understood. However, it should be reasonable to assume that there are two distinct molecular pathways for gastric carcinogenesis by H. pylori infection; the direct action of the bacteria itself on gastric epithelial cells, and the accumulation of genetic changes caused by prolonged bacterial infection and chronic inflammation. As a direct action of H. pylori, bacterial proteins such as CagA could be delivered into gastric epithelial cells via the type IV secretion apparatus and modify the host cell functions related to cell proliferation. In addition to the direct bacterial action, H. pylori infection and the resultant inflammatory response cause various genetic and epigenetic changes in tumor-related genes of the gastric epithelial cells. Notably, expression of AID (activation-induced cytidine deaminase), a DNA editing enzyme that undergoes somatic hypermutation on human genes, is induced in response to H. pylori infection and proinflammatory cytokine stimulation in human gastric epithelial cells. As a result, the accumulation of genetic alterations would persist until the clinical stage of atrophic gastritis and eventually trigger the malignant transformation of gastric cells.
许多流行病学研究已证实幽门螺杆菌（Helicobacter pylori）感染与人类胃癌发生之间存在密切关联。幽门螺杆菌感染诱发胃癌发生的确切机制仍未完全明确。然而，可以合理推测幽门螺杆菌感染导致胃癌发生存在两条不同的分子途径：细菌本身对胃上皮细胞的直接作用，以及长期细菌感染和慢性炎症引起的基因变化积累。作为幽门螺杆菌的直接作用，诸如细胞毒素相关蛋白A（CagA）等细菌蛋白可通过IV型分泌系统传递至胃上皮细胞，并改变与细胞增殖相关的宿主细胞功能。除了细菌的直接作用外，幽门螺杆菌感染及由此产生的炎症反应会导致胃上皮细胞肿瘤相关基因发生各种遗传和表观遗传变化。值得注意的是，在人类胃上皮细胞中，响应幽门螺杆菌感染和促炎细胞因子刺激会诱导激活诱导胞嘧啶脱氨酶（AID）的表达，AID是一种对人类基因进行体细胞超突变的DNA编辑酶。结果，基因改变的积累会持续到萎缩性胃炎临床阶段，并最终引发胃细胞的恶性转化。
