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Helicobacter pylori: gastric cancer and beyond

Nature Reviews Cancer volume 10, pages 403–414 (2010)Cite this article

Subjects

An Erratum to this article was published on 01 August 2010

Key Points

  • Infection with Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, but only a minority of colonized individuals develop cancer of the stomach.

  • H. pylori strains exhibit extensive genetic diversity and strain-specific proteins augment the risk for malignancy.

  • β-catenin signalling has an important role in conjunction with other oncogenic pathways in the regulation of host responses to H. pylori that have carcinogenic potential.

  • Transactivation of epidermal growth factor receptor may help us understand the epithelial signalling pathways that mediate H. pylori-induced carcinogenesis.

  • Chronic inflammation can induce aberrant β-catenin activation in the context of H. pylori infection.

  • A mechanistic understanding of H. pylori activation of oncogenic signalling may lead to key insights into malignancies that arise from inflammatory foci in other organ systems.

Abstract

Helicobacter pylori is the dominant species of the human gastric microbiome, and colonization causes a persistent inflammatory response. H. pylori-induced gastritis is the strongest singular risk factor for cancers of the stomach; however, only a small proportion of infected individuals develop malignancy. Carcinogenic risk is modified by strain-specific bacterial components, host responses and/or specific host–microbe interactions. Delineation of bacterial and host mediators that augment gastric cancer risk has profound ramifications for both physicians and biomedical researchers as such findings will not only focus the prevention approaches that target H. pylori-infected human populations at increased risk for stomach cancer but will also provide mechanistic insights into inflammatory carcinomas that develop beyond the gastric niche.

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Figure 1: Helicobacter pylori VacA structure and functional effects.
Figure 2: Interactions between pathogenic H. pylori and gastric epithelial cells.
Figure 3: Aberrant activation of β-catenin by Helicobacter pylori.
Figure 4: Transactivation of EGFR by H. pylori and induced cellular consequences with carcinogenic potential.

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Authors and Affiliations

  1. Department of Pediatrics, University of Southern California, Los Angeles, 10027, CA, USA

    D. Brent Polk

  2. Department of Medicine, Vanderbilt University, 2215B Garland Avenue, Nashville, 37232–2279, TN, USA

    Richard M. Peek Jr

  3. Department of Cancer Biology, Vanderbilt University, 2215B Garland Avenue, Nashville, 37232–2279, TN, USA

    Richard M. Peek Jr

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Glossary

Chronic superficial gastritis

An early step in the histological cascade proceeding from normal gastric mucosa to intestinal-type gastric cancer. Characterized by the infiltration of the gastric lamina propria with mononuclear and polymorphonuclear inflammatory cells.

Atrophic gastritis

An intermediate histological step in the progression to intestinal-type gastric adenocarcinoma. Characterized by variable gland loss and the encroachment of inflammatory cells into the glandular zones.

Attributable risk

The risk for a particular condition or disease that is defined by differences in the rates of that condition or disease between an exposed group and an unexposed group.

Panmictic population

A microbial population that is not clonal but is characterized by extensive recombination and genetic diversity.

Adaptive immune response

Also known as specific or acquired immunity. It is mediated by antigen-specific lymphocytes and antibodies, is highly antigen-specific and includes the development of immunological memory.

Lewis histo-blood-group antigen

A fucosylated antigen that is expressed on erythrocytes as well as in other body compartments, including the gastric epithelium.

Phase variation

The alteration of bacterial surface proteins (for example, outer membrane proteins, flagella and lipopolysaccharide) to evade the host immune system.

Pilus

Projection from the bacterial cell surface that allows bacteria to attach to other cells to facilitate the transfer of proteins or genetic material.

Lamina propria

A constituent of the moist linings of mucous membranes, which line different tubes of the body, including the gastrointestinal tract.

Polymorphic mosaic gene

A gene that exists as different alleles owing to defined regions that vary in sequence.

Parietal cell

A secretory cell that produces acid and is present within the gastric corpus.

Myeloid-derived suppressor cell (MDSC)

A heterogeneous and plastic cell. When isolated from normal bone marrow, it does not exhibit immunosuppresive effects. However, when exposed to the tumour microenvironment, it inhibits both CD4+ and CD8+ T cells.

Foveolar hyperplasia

Excessive proliferation of epithelial cells within foveolae, small pits from which gastric glands form that result in elongation and tortuosity of the glandular lumen.

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Polk, D., Peek, R. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 10, 403–414 (2010). https://doi.org/10.1038/nrc2857

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