Carcinogenesis of Helicobacter pylori

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 133; no. 2; p. 659
• Main Authors: Correa, Pelayo, Houghton, Jeanmarie
• Format: Journal Article
• Language: English
• Published: United States 01.08.2007
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Anticarcinogenic Agents - pharmacology; Anticarcinogenic Agents - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Bone Marrow Cells - microbiology; Bone Marrow Cells - pathology; Cell Differentiation; Cell Proliferation; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Disease Models, Animal; Disease Progression; Gastric Mucosa - drug effects; Gastric Mucosa - metabolism; Gastric Mucosa - microbiology; Gastric Mucosa - pathology; Helicobacter Infections - complications; Helicobacter Infections - drug therapy; Helicobacter Infections - metabolism; Helicobacter Infections - microbiology; Helicobacter Infections - pathology; Helicobacter pylori; Humans; Mice; Mice, Inbred C57BL; Neoplastic Stem Cells - microbiology; Neoplastic Stem Cells - pathology; Precancerous Conditions - metabolism; Precancerous Conditions - microbiology; Precancerous Conditions - pathology; Precancerous Conditions - prevention & control; Signal Transduction; Stomach Neoplasms - metabolism; Stomach Neoplasms - microbiology; Stomach Neoplasms - pathology; Stomach Neoplasms - prevention & control
• DOI: 10.1053/j.gastro.2007.06.026
• ISSN: 0016-5085

Helicobacter infection is the leading cause of gastric cancer worldwide. Infection with this ubiquitous bacterium incites a chronic active immune response that persists for the life of the host, in the absence of antibiotic-induced eradication. It is the combination of bacterial factors, environmental insults, and the host immune response that drives the initiation and progression of mucosal atrophy, metaplasia, and dysplasia toward gastric cancer. Although it may seem intuitively obvious that removing the offending organism would negate the cancer risk, this approach is neither feasible (half of the world harbors this infection) nor is it straightforward. Most patients are infected in childhood, and present with various degrees of mucosal damage before any therapy. This review outlines the histologic progression of human Helicobacter infection from the early stages of inflammation through the development of metaplasia, dysplasia, and, finally, cancer. The effects of dietary and bacterial eradication therapy on disease progression and lesion reversibility are reviewed within the context of population studies and compared between study designs and populations tested. Eradication studies in the mouse model of infection prevents the formation of gastric cancer, and allows regression of established lesions, providing a useful model to study interaction between bacterium, environment, and host, without the difficulties inherent in human population studies. Recent advances in identifying the bone marrow-derived stem cell as the cell of origin of Helicobacter-induced gastric cancer in the murine model are discussed and interpreted in the context of human disease, and implications for future treatment are discussed.