Relationships between cagA, vacA, and iceA genotypes of Helicobacter pylori and DNA damage in the gastric mucosa

Abstract

Helicobacter pylori (H. pylori) is believed to predispose carriers to gastric cancer by inducing chronic inflammation. The inflammatory processes may result in the generation of reactive oxygen and nitrogen species that damage DNA. In this study, we investigated the relationships between DNA damage in the gastric mucosa and cagA, vacA, and iceA genotypes of H. pylori. The study was conducted with biopsies from the gastric antrum and corpus of 98 H. pylori-infected and 26 uninfected control patients. H. pylori genotypes were determined by PCR and DNA damage was measured in gastric mucosal cells by the Comet assay (single cell gel electrophoresis). All patients were nonsmokers, not abusing alcohol, and not using prescription or recreational drugs. Levels of DNA damage were significantly higher (P < 0.0001) in the H. pylori-infected patients than in uninfected patients. In comparison with the level of DNA damage in the uninfected controls, the extent of DNA damage in both the antrum (OR = 8.45; 95% CI = 2.33-37.72) and the corpus (OR = 6.55; 95% CI = 2.52-17.72) was related to infection by cagA+/vacAs1m1 and iceA1 strains. The results indicate that the genotype of H. pylori is related to the amount of DNA damage in the gastric mucosa. These genotypes could serve as biomarkers for the risk of extensive DNA damage and possibly gastric cancer.

Relationship among Oxidative DNA Damage, Gastric Mucosal Density and the Relevance of cagA, vacA and iceA Genotypes of Helicobacter pylori

“…Our results demonstrate increased levels of oxidative DNA damage in patients infected with cagA + strains. The importance of this oxidative DNA damage has been confirmed by our previously study [7] and by study of Farinati et al [31], that also reported higher levels of oxidative DNA damage in H. pylori-infected patients by cagA + strains. These results may be explained by the continuous induction of DNA damage in the gastric mucosa caused by persistent generation of ROS and RNS in inflammatory processes, and the accumulation of DNA damage due to the inhibition of DNA repair and apoptosis by nitric oxide [32].…”

“…However, this association varies considerably across populations and the scientific evidence is somewhat inconsistent [27]. In the previous study, we investigated the relationships between DNA damage in the gastric mucosa and cagA, vacA, and iceA genotypes of H. pylori without use of enzymes endo III and FPG [7]. Endo III recognizes oxidized pyrimidines, while FPG identifies oxidized purines, especially 8-oxo-guanine.…”

“…The extent and severity of gastric mucosal inflammation, as well as the clinical outcome of the infection, depend on a number of factors, including the host genetic susceptibility, immune response, the age at which the infection was acquired, and environmental factors, especially dietary and factors of the bacterium [3]. The DNA damage level could be determined by positive correlation between inflammatory activity and density of H. pylori [6] or several bacterial virulence genes, such as cytotoxin-associated antigen (cagA), vacuolating cytotoxin (vacA) and induced by contact with epithelium (iceA) [7].…”

Helicobacter pyloriis not associated with anaemia in Latin America: results from Argentina, Brazil, Bolivia, Cuba, Mexico and Venezuela

“…pylori is genetically diverse and type I strains, which are cagA 1 and secrete the vacuolating cytotoxin, are assumed to be the most virulent (61,62) , being associated with the presence of more severe disease (63)(64)(65)(66)(67)(68)(69) . Increased bacterial load could also promote gastric inflammation (70) which therefore could stimulate epithelial damage and increase disease severity.…”

The Biology ofHelicobacter pyloriInfection, a Major Risk Factor for Gastric Adenocarcinoma

“…On the host side, Ladeira et al (23,24) investigated the extent of DNA damage in normal and infected gastric tissue using a single-cell comet assay. They found that DNA damage correlated with H. pylori infection and degree of gastritis.…”