The Helicobacter pylori cagpathogenicity island as a determinant of gastric cancer risk

ABSTRACTHelicobacter pyloristrains can be broadly classified into two groups based on whether they contain or lack a chromosomal region known as the cagpathogenicity island (cagPAI). Colonization of the human stomach with cagPAI-positive strains is associated with an increased risk of gastric cancer and peptic ulcer disease, compared to colonization with cagPAI-negative strains. The cagPAI encodes a secreted effector protein (CagA) and components of a type IV secretion system (Cag T4SS) that delivers CagA and non-protein substrates into host cells. Animal model experiments indicate that CagA and the Cag T4SS stimulate a gastric mucosal inflammatory response and contribute to the development of gastric cancer. In this review, we discuss recent studies defining structural and functional features of CagA and the Cag T4SS and mechanisms by which H. pyloristrains containing the cagPAI promote the development of gastric cancer and peptic ulcer disease.