Interplay between Helicobacter pylori and host gene polymorphisms in inducing oxidative DNA damage in the gastric mucosa

Alberto Izzotti, Silvio De Flora, Cristina Cartiglia, Bianca Maria Are, Mariagrazia Longobardi, Anna Camoirano, Ida Mura, Maria Pina Dore, Antonio Mario Scanu, Paolo Cossu Rocca, Alessandro Maida, Andrea Piana

Research output: Contribution to journalArticlepeer-review

Abstract

Infection by Helicobacter pylori is the most important risk factor for gastric cancer. However, only a small fraction of colonized individuals, representing at least half of the world's population, develop this malignancy. In order to shed light on host-microbial interactions, gastric mucosa biopsies were collected from 119 patients suffering from dyspeptic symptoms. 8-Hydroxy-2′-deoxyguanosine (8-oxo-dG) levels in the gastric mucosa were increased in carriers of H.pylori, detected either by cultural method or by polymerase chain reaction, and were further increased in subjects infected with strains positive for the cagA gene, encoding the cytotoxin-associated protein, cagA. Oxidative DNA damage was more pronounced in males, in older subjects, and in H. pylori-positive subjects suffering from gastric dysplasia. Moreover, 8-oxo-dG levels were significantly higher in a small subset of subjects having a homozygous variant allele of the 8-oxoguanosine-glycosylase 1 (OGG1) gene, encoding the enzyme removing 8-oxo-dG from DNA. Conversely, they were not significantly elevated in glutathione S-transferase M1 (GSTM1)-null subjects. Thus, both bacterial and host gene polymorphisms affect oxidative stress and DNA damage, which is believed to represent a key mechanism in the pathogenesis of gastric cancer. The interplay between bacterial and host gene polymorphisms may explain why gastric cancer only occurs in a small fraction of H. pylori-infected individuals.

Original languageEnglish
Pages (from-to)892-898
Number of pages7
JournalCarcinogenesis
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 2007

ASJC Scopus subject areas

  • Cancer Research

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