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Mechanisms of Disease: Helicobacter pylori-related gastric carcinogenesis—implications for chemoprevention

Nature Clinical Practice Gastroenterology & Hepatology volume 3, pages 622–632 (2006)Cite this article

Abstract

Gastric adenocarcinoma is the second most common cause of cancer-related mortality worldwide. Infection with Helicobacter pylori is the single most common cause of adenocarcinoma of the distal stomach. Cancer risk is believed to be related to differences among H. pylori strains and inflammatory responses governed by host genetics. In particular, specific interactions between host factors that modulate the response to the infection, and bacterial virulence factors that can directly cause tissue damage seem to have a major pathogenic role in the development of gastric cancer. In addition, environmental factors can modify key growth signaling pathways within the gastric mucosa, which leads to the alteration of epithelial cell growth. Preventive strategies represent the most promising means of decreasing cancer risk, and must be aimed at the control of H. pylori infection, improvement of environmental conditions, and the identification of subjects who are genetically predisposed to the development of cancer in response to H. pylori infection. Understanding the intracellular signaling pathways that are specifically affected by H. pylori and that promote phenotypic and genotypic changes that might ultimately progress to malignant transformation could enable physicians to focus eradication therapy appropriately and design interventions targeted at the molecular level to prevent the development of gastric cancer.

Key Points

  • Gastric cancer is still a major health problem worldwide

  • Mounting evidence indicates that H. pylori infection has a major role in the development of adenocarcinoma of the distal stomach

  • H. pylori-related gastric carcinogenesis involves interactions between specific bacterial virulence factors, host genetic susceptibility factors, and environmental factors

  • Preventive strategies include eradication of H. pylori infection, modification of diet to increase the intake of antioxidant micronutrients, and the identification of signaling pathways specifically affected by the bacterium, which might represent molecular targets for intervention

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Figure 1: Signal transduction pathways triggered by H. pylori virulence factors in gastric epithelial cells.

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Acknowledgements

The work performed in authors' laboratories is supported in part by grants from CIRANAD, and Ministero dell'Istruzione, dell' Università e della Ricerca Scientifica e Tecnologica (PRIN 2002 and 2004 to VR and RZ), Italy. The excellent artwork of Mrs Maria Grazia Catenacci is also acknowledged. Restrictions placed on the number of references that could be cited in this review mean that, in many cases, either a single paper or a review is cited. We apologize to those authors whose work has not been cited.

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Authors and Affiliations

  1. Associate Professor of Gastroenterology at the Department of Internal Medicine–Gastroenterology Unit, Second University of Naples, Italy

    Marco Romano

  2. Associate Professor of Physiology at the Department of Experimental Medicine, University of Pavia Medical School, Pavia, Italy

    Vittorio Ricci

  3. Assistant Professor of Hygiene and Public Health at the Department of Preventive Medical Sciences, Medical School of the University of Naples “Federico II”, Naples, Italy

    Raffaele Zarrilli

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  1. Marco Romano
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Correspondence to Marco Romano.

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Romano, M., Ricci, V. & Zarrilli, R. Mechanisms of Disease: Helicobacter pylori-related gastric carcinogenesis—implications for chemoprevention. Nat Rev Gastroenterol Hepatol 3, 622–632 (2006). https://doi.org/10.1038/ncpgasthep0634

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