The Helicobacter pylori cag pathogenicity island as a determinant of gastric cancer risk

ABSTRACT

Helicobacter pylori strains can be broadly classified into two groups based on whether they contain or lack a chromosomal region known as the cag pathogenicity island (cag PAI). Colonization of the human stomach with cag PAI-positive strains is associated with an increased risk of gastric cancer and peptic ulcer disease, compared to colonization with cag PAI-negative strains. The cag PAI 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. pylori strains containing the cag PAI promote the development of gastric cancer and peptic ulcer disease.

KEYWORDS:

• Helicobacter pylori
• gastric cancer
• inflammation
• bacterial secretion system
• effector protein

Acknowledgments

This work was supported by NIH AI118932, AI039657, CA116087, T32 GM008320, and T32 AI112541, and the Department of Veterans Affairs (1I01BX004447).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The work was supported by the National Institutes of Health [T32 AI112541]; National Institutes of Health [T32 GM008320]; National Institutes of Health [AI118932, CA116087, AI039657]; U.S. Department of Veterans Affairs [BX004447].