Variations in Helicobacter pylori Cytotoxin-Associated Genes and Their Influence in Progression to Gastric Cancer: Implications for PreventionReport as inadecuate




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Helicobacter pylori HP is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag cytotoxin-associated genes pathogenicity island cagPAI, a 40 kb stretch of DNA that encodes components of a type IV secretion system T4SS. This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI cagC, cagE, cagL, cagT, cagV and cag Gamma using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing 454 Roche methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs 11 non-synonymous and 14 synonymous showed statistically significant differences P<0.05, and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer p-value = 2.07×10−6, and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations.



Author: Cosmeri Rizzato, Javier Torres, Martyn Plummer, Nubia Muñoz, Silvia Franceschi, Margarita Camorlinga-Ponce, Ezequiel M. Fuentes-

Source: http://plos.srce.hr/



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