53 The cagE genotype has been associated with gastric cancer in some studies,54,55 but contrary results have also been published.56,57 The protein CagA is encoded by the cagA gene situated on the cag pathogenicity island (cag-PAI). This protein is delivered by a specific type IV transporter into the gastric cell cytoplasm, whereupon it induces cell proliferation and division by interacting with target molecules such as the cytoplasmic Src homology 2 domain of Src homology 2 phosphatase (SHP-2).52 Huang et al. performed a meta-analysis Epigenetics Compound Library chemical structure of 16 studies with 2284 cases and 2770 controls to examine the relationship between

CagA seropositivity and the risk of gastric cancer58 and showed that infection with cagA-positive strains of H. pylori increased the risk for gastric cancer over the risk associated with H. pylori infection alone. Individually, H. pylori and cagA seropositivity significantly increased the risk for gastric cancer by 2.28- and 2.87-fold, respectively. However, among H. pylori-infected populations, infection with cagA-positive strains further increased the risk for gastric cancer by 1.64-fold (95%CI,

1.21–2.24) overall and by 2.01-fold (95%CI, 1.21–3.32) for non-cardiac gastric cancer. CagA is characterized by the presence of five repeated amino acid sequences (Glu-Pro-Ile-Tyr-Ala), designated EPIYA Erastin supplier motifs that are located at the C terminus of the protein. Four different EPIYA motifs (EPIYA-A, EPIYA-B, EPIYA-C and EPIYA-D) have been defined and based on the EPIYA motifs and the CagA protein has been classified into Western and Eastern types. The Western type, prevalent in Europe, America, Australia and Africa, contains EPIYA-A and EPIYA-B, followed by up to five repeated sequences of EPIYA-C, whereas the East Asian strain, which is dominant in Japan, Korea and China, possesses EPIYA-A, EPIYA-B, and

EPIYA-D.59 The East Asian strain has been shown to be more virulent than the Western CagA with respect to clinical outcomes. Azuma et al. demonstrated that in the gastric antrum and body, the grades of inflammation, activity and mucosal atrophy were significantly higher in patients infected with Eastern cagA-positive strains than in those infected with Western cagA-positive strains.60 Satomi et al. showed that click here in Okinawa, Japan, where both Western and East Asian CagA were present, 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%). Western strains predominate in patients with duodenal ulcers.61 Similar results were reported by Vilaichone et al. from Thailand, a country regarded as a cultural crossroad between East and South Asia, where the predominant H. pylori genotype changes from East Asian to South Asian.62 In that study, 85% of H.