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  • 1
    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; Germany ; POPULATION ; RISK ; GENE ; GENES ; NITRIC-OXIDE SYNTHASE ; INFECTION ; CARCINOGENESIS ; GENETIC POLYMORPHISMS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; NO ; PROMOTER ; RATES ; VARIABILITY ; HELICOBACTER-PYLORI ; INTERFERON-GAMMA ; inflammation ; ONCOLOGY ; RE ; SNPs ; GRADE ; HELICOBACTER-PYLORI INFECTION ; USA ; nitric oxide synthase ; cyclooxygenase ; PROMOTER VARIANT ; Helicobacter pylori ; HIGH-RISK POPULATION ; VENEZUELA ; NUCLEOTIDE ; ANTRUM ; gastric premalignant lesions ; interferon gamma ; VACA
    Abstract: Chronic inflammation induced by Helicobacter pylori is a key process in gastric carcinogenesis. We hypothesized that genetic polymorphisms in important mediators of H. pylori-induced inflammation may influence the risk of developing various grades of precancerous lesions. We studied the associations between single nucleotide polymorphisms (SNPs) in cyclooxygenase 1 and 2 (PTGS1 and PTGS2), inducible nitric oxide synthase (NOS2A), interferon gamma (IFNG) and its receptor (IFNGR1), and risk of gastric precancerous lesions in a Venezuelan population characterized by high rates of H. pylori infection. We found no association of precancerous lesions with SNPs in PTGS1 and in IFNG. A nonsynonymous SNP of NOS2A (Ser608Leu) and an SNP located in the promoter of IFNGR1 (C-56T) were associated with higher risk of atrophic gastritis [odds ratio (OR)= 1.37, 95% confidence interval (CI)=1.01-1.86, and OR=1.49, 95% CI=1.01-2.19, respectively]. Two SNPs; of PTGS2 were associated with risk of dysplasia (OR = 1.60, 95% CI = 1.01 -2.54, and OR = 0.66, 95% CI = 0.43-0.99). We conclude that genetic variability in the genes we studied does not play a major role in the early stages of gastric carcinogenesis
    Type of Publication: Journal article published
    PubMed ID: 18287876
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  • 2
    Keywords: CANCER ; POPULATION ; RISK ; GENE ; GENES ; GENETIC POLYMORPHISMS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; MUTATIONS ; MYOCARDIAL-INFARCTION ; PREVALENCE ; ULCERATIVE-COLITIS ; CROHNS-DISEASE ; INFLAMMATORY-BOWEL-DISEASE ; ASSOCIATIONS ; PROMOTER POLYMORPHISM ; development ; CD14 GENE ; HELICOBACTER-PYLORI INFECTION ; GENOTYPE ; lipopolysaccharide ; Helicobacter pylori ; stomach cancer ; premalignant lesions ; ASP299GLY POLYMORPHISM ; RECEPTOR-4 GENE
    Abstract: As Helicobacter pylori (HP) is a Gram-negative bacterium, we investigated the associations between several functional polymorphisms in genes involved in lipopolysaccharide (LPS) signaling and the prevalence of various stages of gastric premalignant lesions in a Venezuelan population. The two NOD2 polymorphisms, del3020insC and Gly908Arg, were too infrequent to study their associations with gastric lesions. The risk of intestinal metaplasia (IM) was significantly increased among subjects with the CD14 T-260 allele compared to those without this allele. A similar, but nonsignificant increase in risk for dysplasia was observed among homozygotes of this allele. There was no association between TLR4 Asp299Gly polymorphism and any type of lesions, except for a slight nonsignificant increase in risk of IM associated with the AA genotype among subjects with a higher histological HP score. These results suggest that genetic polymorphisms in HP LPS signaling may be implicated in the development of intermediate stages of gastric premalignant lesions
    Type of Publication: Journal article published
    PubMed ID: 17171451
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  • 3
    Keywords: CANCER ; carcinoma ; DIAGNOSIS ; FOLLOW-UP ; RISK ; GENE ; GENES ; ACCURACY ; DNA ; INFECTION ; MARKER ; CARCINOGENESIS ; ASSOCIATION ; POLYMORPHISMS ; VARIANTS ; TRIAL ; LESIONS ; PROGRESSION ; EXPERIENCE ; DIFFERENCE ; RATES ; POLYMERASE-CHAIN-REACTION ; STOMACH ; INDIVIDUALS ; CHAIN-REACTION ; chemoprevention ; GASTRIC-CANCER ; HELICOBACTER-PYLORI ; BIOPSY ; CHAIN ; ONCOLOGY ; REGRESSION ; RE ; VARIANT ; INCREASE ; polymerase chain reaction ; gastric cancer ; development ; INTERVAL ; methods ; GENOTYPE ; TESTS ; STRAINS ; USA ; odds ratio ; SPECIMENS ; Helicobacter pylori ; BIOPSIES ; LOGISTIC-REGRESSION ; CAGA ; gastric ; HIGH-RISK POPULATION ; VENEZUELA
    Abstract: Background Helicobacter pylori infection is associated with the development of gastric cancer. Although infection with an H. pylori strain containing the cytotoxin-associated (cag A) gene (a marker for a pathogenicity island) may increase the risk of atrophic gastritis and gastric cancer, the relationship of variants in pathogenic H. pylori genes to the severity and progression of precancerous lesions is not well defined. Methods Gastric biopsy specimens were obtained at enrollment from 2145 participants in a chemoprevention trial in Tachira State, Venezuela, and examined histologically to determine the severity of precancerous lesions. The presence of H. pylori DNA in gastric biopsies and the strain type according to presence or absence of the cagA gene were detected by polymerase chain reaction and specific probes. The relationship between H. pylori DNA and histologic diagnosis was analyzed by polytomous logistic regression. Rates of progression and regression of precancerous lesions were determined from biopsies from additional annual gastroscopies (mean follow-up = 3.5 years). All statistical tests were two-sided. Results At enrollment, there was a strong association between cagA-positive H. pylori infection and the severity of gastric precancerous lesions, but cagA-negative H. pylori was associated only with chronic gastritis. Using individuals with normal mucosa or superficial gastritis as control subjects, the odds ratio for dysplasia was 15.5 (95% confidence interval [CI] = 6.42 to 37.2) in cagA-positive individuals compared with uninfected individuals and 0.90 (95% CI = 0.37 to 2.17) for individuals infected with cagA-negative H. pylori compared with uninfected individuals. Individuals infected with cagA-positive H. pylori appeared more likely to experience progression (and less likely to experience regression) of precancerous lesions than those infected with cagA-negative H. pylori, but the differences did not attain statistical significance. Conclusions This large epidemiologic study shows a strong relationship between the presence of H. pylori DNA in gastric biopsies and the severity of precancerous lesions that is specific to cagA-positive strains. The association between H. pylori and gastric carcinoma may have been previously underestimated due to the poor accuracy of serologic H. pylori markers and lack of discrimination by cagA genotype
    Type of Publication: Journal article published
    PubMed ID: 17728213
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