日本京都大学的一个研究小组２日说，幽门螺杆菌之所以能引发胃癌，是因为它能间接使抑制癌症的基因变异失去效用。
研究人员在《自然医学》杂志网络版上报告说，他们在观察感染幽门螺杆菌的胃粘膜时，意外发现其上皮细胞中承担免疫功能的基因“ＡＩＤ”异常活跃。“ＡＩＤ”基因合成的“ＡＩＤ”酶能使“ｐ５３”等基因发生突变，导致后者失去抑制癌症的效用。研究人员用培养的人类胃部细胞进行实验证实，正是幽门螺杆菌感染导致基因“ＡＩＤ”异常活跃。
幽门螺杆菌是胃癌的罪魁祸首，但幽门螺杆菌引发胃癌的具体机制此前一直没有被发现。根据此次研究结果，京都大学的研究人员认为，如果能开发出以“ＡＩＤ”为目标的基因疗法，就有望防止胃癌发生。
人是幽门螺杆菌的唯一自然宿主。据估计，全世界约５０％的人胃部都“藏”有幽门螺杆菌，但只有极少数人会受感染，并因此患上胃炎、胃溃疡或胃癌。
部分英文原文：
Nature Medicine,Published online: 1 April 2007; | doi:10.1038/nm1566
Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium
Yuko Matsumoto1, Hiroyuki Marusawa1, Kazuo Kinoshita2, Yoko Endo1, Tadayuki Kou1, Toshiyuki Morisawa1, Takeshi Azuma3, Il-Mi Okazaki4, Tasuku Honjo4 & Tsutomu Chiba1
1 Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
2 Evolutionary Medicine, Shiga Medical Center Research Institute, 5-4-30, Moriyama, Shiga 524-8524, Japan.
3 Frontier Medical Science in Gastroenterology, International Center for Medical Research and Treatment, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
4 Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Correspondence should be addressed to Tsutomu Chiba chiba@kuhp.kyoto-u.ac.jp
Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IB kinase–dependent nuclear factor-B activation pathway. H. pylori–mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori–associated gastric carcinogenesis.
