Abstract
Helicobacter pylori is a human pathogen that is associated with various severe gastric diseases including gastric and duodenal ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. There are an estimated 800,000 new cases of gastric cancer each year that are attributed to infection with Helicobacter pylori. While several viruses have been linked to cancer development, Helicobacter pylori is the only bacterium to date that has been clearly demonstrated to be a carcinogen. Indeed, Helicobacter pylori is the most important risk factor for development of gastric cancer, and eradication of the bacterium during the early stages of disease significantly reduces the risk of malignant transformation. In most cases, infection occurs during childhood and, if left untreated, usually persists for life. However, most infections with Helicobacter pylori remain asymptomatic or cause mild gastritis. Progression to adenocarcinoma requires infection with more pathogenic strains of Helicobacter pylori and also depends on the genetic predisposition of the host, particularly genes involved in increased inflammatory responses. Environmental factors and diet also play an important role. While many virulence factors of Helicobacter pylori have been described, the CagA toxin, which is translocated into gastric epithelial cells via a bacterial secretion system, appears to be the most specific for the development of a pathological phenotype. In vitro, CagA interferes with many cancer-related signaling pathways, while animal models clearly demonstrate a role for cagA as a putative bacterial oncogene. In this chapter we describe some of the important cancer-related signaling pathways that are triggered by CagA, discuss the importance of the immune response for cancer development, and present animal models that are commonly used to study Helicobacter pylori pathogenesis.
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Acknowledgements
We would like to thank Mr. Steven M. Lane and Dr. Eric Yager for the critical reading of this chapter. M. Stein is supported by a RO1 grant of the National Institute of Health (grant number 1R01CA160790-01A1).
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Mishra, J., Ruggiero, P., Bagnoli, F., Rappuoli, R., Stein, M. (2015). Helicobacter pylori: The Cancer Bug. In: Shurin, M., Thanavala, Y., Ismail, N. (eds) Infection and Cancer: Bi-Directorial Interactions. Springer, Cham. https://doi.org/10.1007/978-3-319-20669-1_10
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