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

Izzotti, Alberto and De Flora, Silvio and Cartiglia, Cristina and Are, Bianca Maria and Longobardi, Maria Grazia and Camoirano, Anna and Mura, Ida Iolanda and Dore, Maria Pina and Scanu, Antonio Mario and Cossu Rocca, Paolo Alessandro and Maida, Alessandro and Piana, Andrea Fausto (2007) Interplay between Helicobacter pylori and host gene polymorphisms in inducing oxidative DNA damage in the gastric mucosa. Carcinogenesis, Vol. 28 (4), p. 892-898. eISSN 1460-2180. Article.

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DOI: 10.1093/carcin/bgl208

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-20-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.

Item Type:Article
ID Code:516
Status:Published
Refereed:Yes
Uncontrolled Keywords:Helicobacter pylori, gastric cancer, gastric mucosa, oxidative DNA, gastric dysplasia
Subjects:Area 06 - Scienze mediche > MED/42 Igiene generale e applicata
Area 06 - Scienze mediche > MED/12 Gastroenterologia
Area 06 - Scienze mediche > MED/08 Anatomia patologica
Area 06 - Scienze mediche > MED/18 Chirurgia generale
Divisions:001 Università di Sassari > 03 Istituti > Clinica medica generale e terapia medica
001 Università di Sassari > 03 Istituti > Clinica chirurgica generale e terapia chirurgica
001 Università di Sassari > 03 Istituti > Anatomia patologica
001 Università di Sassari > 03 Istituti > Igiene e medicina preventiva
Publisher:Oxford University Press
eISSN:1460-2180
Deposited On:18 Aug 2009 10:02

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