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

Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132, Genoa, Italy.
Carcinogenesis (Impact Factor: 5.27). 05/2007; 28(4):892-8. DOI: 10.1093/carcin/bgl208
Source: PubMed

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.

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    • "pylori) infection is a major risk factor [4] [5]. Increasing evidence has shown that cagA protein, an important H. pylori-produced virulent factor for gastric mucosa injury, could induce many kinds of DNA damage including DNA base damage, DNA double-strand break (DSBs), and oxidative damage [5] [6] [7] [8] [9] [10]. Among these DNA damages, DSBs are the most detrimental form [11] [12], because they may lead to both chromosomal breakage and rearrangement and ultimately lead to tumorigenesis of cancers such as GAA. "
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    ABSTRACT: The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. To determine whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated with Helicobacter pylori (H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we conducted a hospital-based case-control study, including 642 patients with pathologically confirmed GAA and 927 individually matched controls without any evidence of tumours or precancerous lesions, among Guangxi population. Increased risks of GAA were observed for individuals with cagA positive (odds ratio (OR) 6.38; 95% confidence interval (CI) 5.03-8.09). We also found that these individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG) featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did appear to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 15.74 (10.89-22.77) for XRCC7-TG and 38.49 (22.82-64.93) for XRCC7-GG, respectively. Additionally, this polymorphism multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC risk (ORinteraction = 1.49). These results suggest that XRCC7P may be associated with the risk of Guangxiese GAA related to cagA.
    11/2013; 2013:124612. DOI:10.1155/2013/124612
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    • "For some chronic infections, tissues may remain infected for decades, encountering multiple rounds of inflammation and necrosis/ wounding followed by healing. Hence, the cancer risk would be amplified at each cycle (Ames et al., 1995; Mostafa et al., 1999; Friedberg et al., 2006; Lu et al., 2006; Izzotti et al., 2007). The connection between chronic infection, resulting in persistent inflammation, and cancer has been clearly documented for a few infectious diseases. "
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    ABSTRACT: An accumulating body of research indicates there is an increased cancer risk associated with chronic infections. The genus Mycobacterium contains a number of species, including M. tuberculosis, which mount chronic infections and have been implicated in higher cancer risk. Several non-tuberculosis mycobacterial species, including M. marinum, are known to cause chronic infections in fish and like human tuberculosis, often go undetected. The elevated carcinogenic potential for fish colonies infected with Mycobacterium spp. could have far reaching implications because fish models are widely used to study human diseases. Japanese medaka (Oryzias latipes) is an established laboratory fish model for toxicology, mutagenesis, and carcinogenesis; and produces a chronic tuberculosis-like disease when infected by M. marinum. We examined the role that chronic mycobacterial infections play in cancer risk for medaka. Experimental M. marinum infections of medaka alone did not increase the mutational loads or proliferative lesion incidence in all tissues examined. However, we showed that chronic M. marinum infections increased hepatocellular proliferative lesions in fish also exposed to low doses of the mutagen benzo[a]pyrene. These results indicate that chronic mycobacterial infections of medaka are acting as tumor promoters and thereby suggest increased human risks for cancer promotion in human populations burdened with chronic tuberculosis infections.
    Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 03/2009; 149(2-149):152-160. DOI:10.1016/j.cbpc.2008.09.011 · 2.83 Impact Factor
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    • "Infection with H. pylori is the main risk factor for peptic ulcer disease and is correlated with gastritis and cancer ventriculi as well. H. pylori is a common infection all over the world and about half of the world population is believed to be infected, and with highest prevalence in developing countries [4]. There is evidence that eradication of H. pylori infection may be appropriate and beneficial in some dyspeptic patients without peptic ulcer disease [5]. "
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    ABSTRACT: Helicobacter pylori infection is associated with peptic ulcer disease, gastritis, and cancer ventriculi, which can all cause dyspepsia. The diffuse and non-specific symptoms related to dyspepsia renders choice of optimal diagnostic strategy diffi-cult. A Bayesian model and a graphical user interface have been developed to serve as a decision support system for the general practitioner to choose the optimal diagnostic strategy. The model uses known symptoms and risk factors associated with Helicobacter pylori infection along with medicine and diagnostic test results to estimate the chance of infection. The model results have been compared against estimates from two clinical experts in four patient scenarios. The system was tested in a usability test. There were differences between the estimates from the clinical experts and between each expert and the model. The graphical user interface was comprehens-ible and easy to use. The results indicate that the system may be a relevant tool for the general practitioner. Further model refinements and tests are required to conclude on the accura-cy of the model and the clinical impact of the system.
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