Relationship between the diversity of the cagA gene of Helicobacter pylori and gastric cancer in Okinawa, Japan
Relationship between the diversity of the cagA gene of Helicobacter pylori and gastric cancer in Okinawa, Japan
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DOI：
10.1007/s00535-006-1838-6
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发表时间：
2006-06-01
影响因子：
6.3
通讯作者：
Azuma, Takeshi
中科院分区：
文献类型：
--
作者：
Satomi, Satoko;Yamakawa, Akiyo;Azuma, Takeshi
背景。幽门螺杆菌CagA蛋白被认为是与胃癌相关的毒力因子之一。 CagA被注射到胃上皮细胞中，发生酪氨酸磷酸化，并与含有Src同源2结构域的蛋白酪氨酸磷酸酶（SHP-2）结合。在 SHP-2 结合位点中观察到了 CagA 的两种主要亚型，即西亚型和东亚型。东亚型 CagA 与 SHP-2 的结合比西方型 CagA 更强。 CagA 的多样性共同决定了 CagA 与 SHP-2 的结合亲和力，可能是决定不同幽门螺杆菌菌株感染的临床结果的重要变量。方法。我们在日本冲绳调查了 CagA 多样性与临床结果之间的关系。总共研究了24个菌株，其中13个胃癌菌株和11个十二指肠溃疡菌株。我们对全长 cagA 基因进行了测序，并分析了冲绳分离株与先前鉴定的西方幽门螺杆菌菌株之间的系统发育关系。结果。所有检查的分离株均为 cagA 阳性。胃癌患者中东亚CagA阳性菌株的患病率（84.6%）显着高于十二指肠溃疡患者（27.3%）（卡方 = 8.06，P = 0.011）。系统发育分析表明，所有具有东亚型CagA的胃癌菌株均属于东亚型簇，而大多数十二指肠溃疡菌株属于西方型簇。结论。胃癌菌株和十二指肠溃疡菌株的幽门螺杆菌分离株来源不同，东亚CagA阳性幽门螺杆菌感染与胃癌相关。在冲绳观察到的菌株多样性可能会影响日本幽门螺杆菌感染相关疾病的患病率差异。
Background. Helicobacter pylori CagA protein is considered to be one of the virulence factors associated with gastric cancer. CagA is injected into gastric epithelial cells, undergoes tyrosine phosphorylation, and binds to Src homology 2 domain-containing protein-tyrosine phosphatase (SHP-2). Two major subtypes of CagA have been observed in the SHP-2-binding site, the Western and East Asian types. The East Asian-type CagA binds to SHP-2 more strongly than the Western-type CagA. The diversity of CagA, which collectively determines the binding affinity of CagA to SHP-2, may be an important variable in determining the clinical outcome of infection by different H. pylori strains. Methods. We investigated the relationship between the diversity of CagA and clinical outcome in Okinawa, Japan. A total 24 strains, 13 gastric cancer strains and 11 duodenal ulcer strains, were studied. We sequenced full-length cagA genes and analyzed the phylogenetic relationships between Okinawa isolates and previously characterized Western H. pylori strains. Results. All isolates examined were cagA positive. The prevalence of East Asian CagA-positive strains was significantly higher in patients with gastric cancer (84.6%) than in patients with duodenal ulcer (27.3%) (chi-squared = 8.06, P = 0.011). The phylogenetic analysis showed that all gastric cancer strains with East Asian-type CagA were in the East Asian cluster, and that most duodenal ulcer strains were in the Western cluster. Conclusions. The origins of H. pylori isolates are different between gastric cancer strains and duodenal ulcer strains, and East Asian CagA-positive H. pylori infection is associated with gastric cancer. The strain diversity observed in Okinawa may affect the difference in the prevalence of disease associated with H. pylori infection in Japan.