Genetic host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms |
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Authors: | Michiel C Mommersteeg Jun Yu Maikel P Peppelenbosch Gwenny M Fuhler |
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Institution: | 1. Department of Gastroenterology and Hepatology, Erasmus MC University Medical center Rotterdam, Office NA-619, PO Box 2040, 3000 CA Rotterdam, The Netherlands;2. Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences and CUHK-Shenzhen Research Institute, Rm 707A, 7/F., Li Ka Shing Medical Science Building, The Chinese University of Hong Kong, Hong Kong |
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Abstract: | Helicobacter Pylori is a gram negative rod shaped microaerophilic bacterium that colonizes the stomach of approximately half the world's population. Infection with c may cause chronic gastritis which via a quite well described process known as Correas cascade can progress through sequential development of atrophic gastritis, intestinal metaplasia and dysplasia to gastric cancer. H. pylori is currently the only bacterium that is classified as a class 1 carcinogen by the WHO, although the exact mechanisms by which this bacterium contributes to gastric carcinogenesis are still poorly understood. Only a minority of H. pylori-infected patients will eventually develop gastric cancer, suggesting that host factors may be important in determining the outcome of H. pylori infection. This is supported by a growing body of evidence suggesting that the host genetic background contributes to risk of H. pylori infection and gastric carcinogenesis. In particular single nucleotide polymorphisms in genes that influence bacterial handling via pattern recognition receptors appear to be involved, further strengthening the link between host risk factors, H. pylori incidence and cancer. Many of these genes influence cellular pathways leading to inflammatory signaling, inflammasome formation and autophagy. In this review we summarize known carcinogenic effects of H. pylori, and discuss recent findings that implicate host genetic pattern recognition pathways in the development of gastric cancer and their relation with H. pylori. |
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Keywords: | Helicobacter pylori Stomach neoplasms Toll-like receptors NOD-like receptor Polymorphism single nucleotide Autophagy |
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