Helicobacter pylori CagA protein variation associated with gastric cancer in Asia.

Recent molecular analysis has provided the pathological actions of CagA on gastric epithelial cells. CagA is injected into epithelial cells via the type IV secretion system and undergoes tyrosine phosphorylation in the cells. In addition, translocated CagA forms a physical complex with SHP-2. There are two major CagA subtypes; the East Asian and the Western type. The East Asian CagA protein possesses stronger SHP-2 binding activity than the Western CagA. The grades of inflammation, activity of gastritis, and atrophy are significantly higher in gastritis patients infected with the East Asian CagA-positive strain than in gastritis patients infected with the cagA-negative or Western CagA-positive strains. The prevalence of the East Asian CagA-positive strain is associated with the mortality rate of gastric cancer in Asia. Endemic circulation of H. pylori populations carrying biologically more active CagA proteins in East Asian countries, where the mortality rate of gastric cancer is among the highest in the world, may be involved in increasing the risk of gastric cancer in these populations.