Journal Article

Interplay between <i>Helicobacter pylori</i> 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 and Andrea Piana

in Carcinogenesis

Volume 28, issue 4, pages 892-898
Published in print November 2006 | ISSN: 0143-3334
Published online April 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl208
Interplay between Helicobacter pylori and host gene polymorphisms in inducing oxidative DNA damage in the gastric mucosa

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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.

Journal Article.  5582 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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