Relationship between the diversity of the cagA gene of Helicobacter pylori and gastric cancer in Okinawa, Japan.
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.
Satomi
Satoko
S
Second Department of Internal Medicine, Faculty of Medical Science, University of Fukui, Fukui, Japan.
Yamakawa
Akiyo
A
Matsunaga
Shinsuke
S
Masaki
Ryuho
R
Inagaki
Tomoko
T
Okuda
Tomoyuki
T
Suto
Hiroyuki
H
Ito
Yoshiyuki
Y
Yamazaki
Yukinao
Y
Kuriyama
Masaru
M
Keida
Yoshihide
Y
Kutsumi
Hiromu
H
Azuma
Takeshi
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000145:classification / Q000235:genetics*; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics*; D004381:Duodenal Ulcer / Q000453:epidemiology / Q000382:microbiology*; D005260:Female; D014644:Genetic Variation; D016481:Helicobacter Infections / Q000453:epidemiology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D015995:Prevalence; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000382:microbiology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori