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.
BACKGROUND:Helicobacter pyloriCagA 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. pyloriinfection is associated with gastric cancer. The strain diversity observed in Okinawa may affect the difference in the prevalence of disease associated with H. pyloriinfection in Japan.
Authors: J F Tomb; O White; A R Kerlavage; R A Clayton; G G Sutton; R D Fleischmann; K A Ketchum; H P Klenk; S Gill; B A Dougherty; K Nelson; J Quackenbush; L Zhou; E F Kirkness; S Peterson; B Loftus; D Richardson; R Dodson; H G Khalak; A Glodek; K McKenney; L M Fitzegerald; N Lee; M D Adams; E K Hickey; D E Berg; J D Gocayne; T R Utterback; J D Peterson; J M Kelley; M D Cotton; J M Weidman; C Fujii; C Bowman; L Watthey; E Wallin; W S Hayes; M Borodovsky; P D Karp; H O Smith; C M Fraser; J C Venter Journal: Nature Date: 1997-08-07 Impact factor: 49.962
Authors: S Backert; E Ziska; V Brinkmann; U Zimny-Arndt; A Fauconnier; P R Jungblut; M Naumann; T F Meyer Journal: Cell Microbiol Date: 2000-04 Impact factor: 3.715
Authors: M J Blaser; G I Perez-Perez; H Kleanthous; T L Cover; R M Peek; P H Chyou; G N Stemmermann; A Nomura Journal: Cancer Res Date: 1995-05-15 Impact factor: 12.701
Authors: Ramelah Mohamed; Alfizah Hanafiah; Isa M Rose; Mohd Rizal A Manaf; Shiekh Anwar Abdullah; Ismail Sagap; A van Belkum; Jasmi A Yaacob Journal: Eur J Clin Microbiol Infect Dis Date: 2009-02-27 Impact factor: 3.267