TheHelicobacter pylori vacA s1, m1 genotype andcagA is associated with gastric carcinoma in Germany

Miehlke, Stephan; Kirsch, Christian; Agha‐Amiri, Karin; Günther, Thomas; Lehn, Norbert; Malfertheiner, Peter; Stolte, Manfred; Ehninger, Gerhard; Bayerdörffer, Ekkehard

doi:10.1002/1097-0215(20000801)87:3<322::aid-ijc3>3.0.co;2-m

Cited by 133 publications

(29 citation statements)

References 30 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared with toxigenic strains of H. pylori, non-toxigenic vacA s2/m2 strains are associated with a much lower risk of peptic ulceration and gastric adenocarcinoma (31,36,37,50). In this study we have shown why vacA s2/m2 strains are non-toxigenic, the primary determinant being a 12-amino acid N-terminal extension on the VacA protein, which blocks toxin activity regardless of production level or p58 binding region type.…”

Section: Discussionmentioning

confidence: 68%

Determinants of Non-toxicity in the Gastric Pathogen Helicobacter pylori

Letley

Rhead

Twells

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

The Helicobacter pylori vacuolating cytotoxin gene, vacA, is naturally polymorphic, the two most diverse regions being the signal region (which can be type s1 or s2) and the mid region (m1 or m2). Previous work has shown which features of vacA make peptic ulcer and gastric cancer-associated type s1/m1 and s1/m2 strains toxic. vacA s2/m2 strains are associated with lower peptic ulcer and gastric cancer risk and are non-toxic. We now define the features of vacA that determine the nontoxicity of these strains. To do this, we deleted parts of vacA and constructed isogenic hybrid strains in which regions of vacA were exchanged between toxigenic and non-toxigenic strains. We showed that a naturally occurring 12-amino acid hydrophilic N-terminal extension found on s2 VacA blocks vacuolating activity as its removal (to make the strain s1-like) confers activity. The mid region of s2/m2 vacA does not cause the non-vacuolating phenotype, but if VacA is unblocked, it confers cell line specificity of vacuolation as in natural s1/m2 strains. Chromosomal replacement of vacA in a nontoxigenic strain with vacA from a toxigenic strain confers full vacuolating activity proving that this activity is entirely controlled by elements within vacA. This work defines why H. pylori strains with different vacA allelic structures have differing toxicity and provides a rational basis for vacA typing schemes.

show abstract

Section: Discussionmentioning

confidence: 68%

Determinants of Non-toxicity in the Gastric Pathogen Helicobacter pylori

Letley

Rhead

Twells

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Strains containing type s1, i1, or m1 alleles within the 5′ region of the gene are highly associated with GC. 18–20 Host polymorphisms in IL-1β and TNF-α as well as environmental factors such as a high salt diet and low iron levels in the context of H. pylori infection also influence gastric carcinogenesis. 15 …”

Section: Bacterial and Host Factors Affecting The Propensity Toward Gmentioning

confidence: 99%

The Role of the Microbiome in Gastrointestinal Cancer

Wroblewski

Peek

Coburn

2016

Gastroenterology Clinics of North America

View full text Add to dashboard Cite

Humans are host to complex microbial communities that were previously termed “normal flora” and largely overlooked. However, it is increasingly understood that resident microbes contribute to both health and disease, including the risk for malignancy. Investigators are just beginning to define microbes, or groups of microbes, that contribute to the development of gastrointestinal malignancies and the mechanisms by which this occurs. Resident microbes can induce inflammation, leading to cell proliferation and altered stem cell dynamics, which can lead to alterations in DNA integrity and immune regulation and thus promote carcinogenesis. Studies in human patients and rodent models of cancer have identified alterations in the microbiota of the stomach, esophagus, and colon that increase the risk for malignancy. Manipulation of the composition and/or function of the gastrointestinal microbiota could allow for the prevention or treatment of certain gastrointestinal malignancies in the future.

show abstract

“…Although located in different genomic regions, the cagA gene is strongly associated with the cytotoxic activity of VacA,77 and strains expressing the combination of these alleles and cagA are considered the most virulent,78,79 causing more severe epithelial damage,80,81 which can be associated with the development of the most severe gastric diseases.…”

Section: Cagpaimentioning

confidence: 99%

Virulence Factors of Helicobacter pylori: A Review

Röesler

Rabelo-Gonçalves

Zeitune

2014

Clin Med Insights Gastroenterol

134

102

View full text Add to dashboard Cite

Helicobacter pylori is a spiral-shaped Gram-negative bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa, a condition that affects the relative risk of developing various clinical disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. H. pylori presents a high-level of genetic diversity, which can be an important factor in its adaptation to the host stomach and also for the clinical outcome of infection. There are important H. pylori virulence factors that, along with host characteristics and the external environment, have been associated with the different occurrences of diseases. This review is aimed to analyzing and summarizing the main of them and possible associations with the clinical outcome.

show abstract

TheHelicobacter pylori vacA s1, m1 genotype andcagA is associated with gastric carcinoma in Germany

Cited by 133 publications

References 30 publications

Determinants of Non-toxicity in the Gastric Pathogen Helicobacter pylori

Determinants of Non-toxicity in the Gastric Pathogen Helicobacter pylori

The Role of the Microbiome in Gastrointestinal Cancer

Virulence Factors of Helicobacter pylori: A Review

Contact Info

Product

Resources

About