Helicobacter Pylori Cytotoxin-Associated Gene A (CagA) and Gastric Carcinoma

Gastric cancer is a highly lethal disease. Establishment of H. pylori infection as a risk factor for this malignancy help identifying persons at increased risk. Studying the association between the genotypes of H pylori virulence factors and gastric carcinoma would have clinical implications in selecting patients who would benefit from H. pylori eradication treatment, with a subsequent reduced risk of gastric cancer. Many virulence factors are involved in the pathogenicity of H. pylori, including urease, vacuolating cytotoxin (a product of the vacA gene), and the immunogenic protein cagA, encoded by the cytotoxin-associated gene A (cagA). These virulence factors interact and modulate different cellular signaling pathways to induce a pro-inflammatory response or alter tight junctions and cell polarity, which finally favor metastasis. The cagA gene is a virulence gene located in the cag pathogenicity island of the bacterial genome and is frequently associated with more severe clinical outcomes. The cagA proteins can increase the virulence potencies of strains, by increasing host-cell cytokine production and altering protein tyrosine phosphorylation. Many studies revealed a possible association between H. pylori virulence factor cagA and its genotypes and the development of gastric carcinoma among patients, which would help in minimizing the risk of gastric carcinoma development by selecting patients who would benefit from H. pylori eradication. This review highlights how the upregulation of cagA gene could be a risk factor for developing gastric carcinoma and its potential relationship on the selection of patients who would benefit from H. Pylori treatment. Keywords:Cancer, cytokine, virulence