Carcinogenesis Advance Access originally published online on November 24, 2006
Carcinogenesis 2007 28(4):892-898; doi:10.1093/carcin/bgl208
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Interplay between Helicobacter pylori and host gene polymorphisms in inducing oxidative DNA damage in the gastric mucosa
1 Department of Health Sciences, University of Genoa Via A. Pastore 1, I-16132, Genoa, Italy
2 Institute of Hygiene and Preventive Medicine, University of Sassari 07100 Sassari, Italy
3 Institute of General Medical Clinic and Medical Therapy, University of Sassari 07100 Sassari, Italy
4 Institute of Surgical Clinic, University of Sassari 07100 Sassari, Italy
5 Institute of Anatomy and Histopathology, University of Sassari 07100 Sassari, Italy
*To whom correspondence should be addressed. Tel: +39 010 3538500; Fax: +39 010 3538504; E-mail: sdf{at}unige.it
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.
Abbreviations: H.pylori, Helicobacter pylori; 8-oxo-dG, 8-hydroxy-2'-deoxyguanosine; GSTM1, glutathione S-transferase M1; OGG1, 8-oxoguanosine-glycosylase 1; ROS, reactive oxygen species
Received September 20, 2006; revised October 18, 2006; accepted October 20, 2006.
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