Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Sep 8;282(1):1-8.
doi: 10.1016/j.canlet.2008.11.016. Epub 2008 Dec 25.

Helicobacter pylori virulence factors in gastric carcinogenesis

Sicheng Wen  1 , Steven F Moss
Affiliations
Review

Helicobacter pylori virulence factors in gastric carcinogenesis

Sicheng Wen et al. Cancer Lett. .

Abstract

Helicobacter pylori infection is the most important risk factor in the development of non-cardia gastric adenocarcinoma; host genetic variability and dietary co-factors also modulate risk. Because most H. pylori infections do not cause cancer, H. pylori heterogeneity has been investigated to identify possible virulence factors. The strongest candidates are genes within the cag (cytotoxin-associated antigen) pathogenicity island, including the gene encoding the CagA protein, as well as polymorphic variation in the VacA vacuolating exotoxin and the blood group antigen binding adhesin BabA. Improved understanding of the pathogenesis of H. pylori-associated gastric cancer may improve risk stratification for prevention and therapy.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest Statement

None Declared

Figures

None
The pathogenesis of H. pylori infection. Virulence factors such as CagA, genes within the cag PAI, VacA, BabA and SabA are involved in numerous host cell effects. H. pylori adherence to gastric epithelial cells is mediated by BabA and SabA binding Lewisb, and Lewisx/a respectively, thus facilitating H. pylori colonization and the efficient delivery of virulence factors to host cells. Following the attachment of H. pylori to gastric epithelial cell, the CagA protein is delivered into gastric epithelial cells through the H. pylori type 4 secretion system (T4SS). There, CagA may be tyrosine phosphorylated at EPIYA sites initially by SRC and in more sustained fashioned by ABL kinases. CagA can interact with intracellular proteins and deregulate distinct signaling pathways through both tyrosine phosphorylation-dependent or independent mechanisms. The pathobiological effects including cell elongation (producing cell scattering and the “hummingbird” phenotype), disruption of intercellular junctions, loss of cell polarity, the promotion of inflammation and dysregulation of proliferation and apoptosis. The effects of VacA on host cells include induction of cytoplasmic vacuolation, mitochondrial damage, cytochrome c release, apoptosis and immune evasion. Many of these events may contribute to gastric carcinoma development.
See this image and copyright information in PMC

References

    1. Talley NJ, Fock KM, Moayyedi P. Gastric Cancer Consensus conference recommends Helicobacter pylori screening and treatment in asymptomatic persons from high-risk populations to prevent gastric cancer. Am J Gastroenterol. 2008;103:510–514. - PubMed
    1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. - PubMed
    1. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;18:581–592. - PubMed
    1. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–789. - PubMed
    1. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118:3030–3044. - PubMed

Publication types

MeSH terms