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  • DKFZ Publication Database  (6)
  • antibody  (6)
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  • DKFZ Publication Database  (6)
  • 1
    Keywords: PROTEINS ; INFECTION ; CARCINOGENESIS ; antibody ; ADENOCARCINOMAS ; multiplex serology ; CAGA ; ERADICATION ; SHANGHAI WOMENS HEALTH
    Abstract: Background: Helicobacter pylori is the leading risk factor for gastric cancer, yet only a fraction of infected individuals ever develop neoplasia. Methods: To identify potential predictive biomarkers, we assessed the association of 15 antibodies to H. pylori proteins and gastric cancer in a nested case-control study. Blood levels of antibodies were assessed using multiplex serology for 226 incident cases and 451 matched controls from the Shanghai Men's Health Study. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Seropositivity to four (Omp, HP0305, HyuA, and HpaA) proteins was associated with a 1.5- to 3-fold increased risk for gastric cancer. When exCIuding cases diagnosed within 2 years of study enrollment, seropositivity to two additional proteins (CagA and VacA) showed significant associations with risk. Compared with individuals with three or fewer seropositive results to the six virulent proteins identified in this population, individuals with four to five seropositive results were at a 2-fold increased risk (OR, 2.08; 95% CI, 1.31-3.30) and individuals seropositive to all six proteins had a 3.5-fold increase in risk (OR, 3.49; 95% CI, 2.00-6.11) for gastric cancer. Among individuals diagnosed at least 2 years after study enrollment, these associations were even stronger (ORs, 2.79 and 4.16, respectively). Conclusions: Increasing number of seropositives to six H. pylori proteins may be a risk marker for distal gastric cancer in China. Impact: In a population with a 90% prevalence of CagA-positive H. pylori infection, assessment of additional virulent H. pylori proteins might better identify individuals at high risk for gastric cancer.
    Type of Publication: Journal article published
    PubMed ID: 23035179
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  • 2
    Keywords: CANCER ; COMBINATION ; Germany ; POPULATION ; RISK ; GENE ; PROTEIN ; PROTEINS ; INFECTION ; ANTIGEN ; ANTIGENS ; ASSOCIATION ; IMMUNE-RESPONSES ; antibody ; IDENTIFICATION ; PROGRESSION ; WOMEN ; MEN ; GASTRIC-CANCER ; SERUM ; VIRULENCE ; USA ; INCREASED RISK ; RISK-FACTOR ; EXTENT ; PRECURSOR ; BACTERIA ; CAGA ; chronic atrophic gastritis ; IMMUNOPROTEOMICS ; INFECTED PATIENTS ; VIRULENCE FACTORS
    Abstract: Infection with Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG), a precursor lesion of intestinal gastric cancer. The pathogenicity of the bacterium is thought to play an important role in determining the extent and severity of clinical outcome. We aimed to assess the associations between CAG and the serostatus of antibodies to 15 H. pylori proteins. The analyses were based on 534 cases with serologically defined CAG and 1,068 age-matched and sex-matched controls participating in a population-based study conducted in Saarland, Germany among 9,953 men and women ages 50 to 74 years. A newly developed H. pylori multiplex serology method was used to detect antibodies specific to 15 H. pylori antigens. Significant associations were observed between seropositivity for all 15 specific antibodies and the presence of CAG. Exclusion of severe cases, who might have lost the infection in the course of CAG progression, substantially increased the observed associations. In H. pylori-seropositive subjects, cytotoxin-associated gene A (CagA), vacuolating toxin (VacA), helicobacter cysteine-rich protein C (HcpC), and the chaperonin GroEL were identified as independent virulence factors for CAG with adjusted odds ratios (95% confidence interval) of 3.52 (2.01-6.10), 3.19 (1.44-7.05), 4.03 (1.53-10.65), and 2.65 (1.06-6.62), respectively; the simultaneous presence of all four independent virulence factors was associated with an 18-fold risk of CAG. In conclusion, HcpC and GroEL were identified as new independent virulence factors, and in combination with the established virulence factors, CagA and VacA, were strongly associated with CAG. [Cancer Res 2009;69(7):2973-80]
    Type of Publication: Journal article published
    PubMed ID: 19318564
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  • 3
    Keywords: CANCER ; Germany ; QUANTIFICATION ; RISK ; PROTEIN ; PROTEINS ; INFECTION ; MARKER ; ANTIGEN ; ANTIGENS ; ASSOCIATION ; antibodies ; antibody ; IDENTIFICATION ; MARKERS ; cancer risk ; INDIVIDUALS ; PREDICTORS ; GASTRIC-CANCER ; METAANALYSIS ; USA ; RISK STRATIFICATION ; CANCER-RISK ; CAGA ; chronic atrophic gastritis ; BODY GASTRITIS ; CONFIDENCE ; VIRULENCE FACTORS ; IMMUNOBLOT
    Abstract: Infection with Helicobacter pylori is a major cause of gastric cancer (GC). The association likely has been underestimated in the past due to disease-related clearance of the infection. On the other hand, only a minority of the infected individuals develop GC, and better risk stratification is therefore highly desirable. We aimed to assess the association of GC with antibodies to 15 individual H. pylori proteins, determined by novel multiplex serology, to identify potentially relevant risk markers. This analysis was based on 123 GC cases aged 50 to 74 years and 492 age-matched and sex-matched controls from Saarland, Germany. Eight of the antibodies were significantly associated Kith noncdardia GC and seven of them were significantly related to GC at any site. More pronounced associations were observed for noncardia GC; adjusted odds ratios (95% confidence intervals) ranged from 1.60 (1.01-2.54) for HyuA to 5.63 (3.20-9.91) for cytotoxin-associated antigen A (CagA). A dose-response relationship was found between the number of seropositivities and GC (P 〈 0.001). The seropositivities of CagA and GroEL were found to be independent predictors of GC, which were strongly related to GC risk in a dose-response manner (P 〈 0.001). In conclusion, GroEL was identified as a new independent risk marker that may contribute to enhanced quantification of H. pylori-related GC risk. [Cancer Res 2009;69(15):6164-70]
    Type of Publication: Journal article published
    PubMed ID: 19602590
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  • 4
    Keywords: Helicobacter pylori ; serology ; microbiology ; HELICOBACTER-PYLORI ; PATTERN ; PATTERNS ; antibodies ; antibody
    Type of Publication: Meeting abstract published
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  • 5
    Keywords: USA ; chronic atrophic gastritis ; antibody ; antibodies ; ASSOCIATION ; SERUM ; PROTEIN ; PROTEINS
    Type of Publication: Meeting abstract published
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  • 6
    Keywords: CANCER ; COHORT ; POPULATION ; RISK ; INFECTION ; antibody ; adenocarcinoma ; GASTRIC-CANCER ; FOOD FREQUENCY QUESTIONNAIRE ; multiplex serology ; ESOPHAGEAL ; ATROPHIC GASTRITIS ; VIRULENCE FACTORS ; PEPTIC-ULCER ; SOUTHERN COMMUNITY COHORT
    Abstract: Background: Gastric cancer incidence in African Americans is twice that of whites, and differing prevalence of Helicobacter pylori strain-specific isolates may help explain the disparity. Methods: Serum levels of antibodies to each of 15 H. pylori proteins were assessed using multiplex serology for a sample of 689 African American and white participants from the Southern Community Cohort Study. African and European admixture was estimated using a panel of 276 ancestry genetic markers, with "low," "medium," and "high" categories of African ancestry defined as 〈 85%, 85% to 95%, and 〉= 95%. Results: The majority (79%) of our study population were sero-positive for H. pylori. African American race was associated with a two-to sixfold increased odds for sero-positivity to eight H. pylori proteins, including the cancer-associated virulence constituents CagA [odds ratio (OR), 6.4; 95% CI, 4.5-9.1], and VacA (OR, 2.3; 95% CI, 1.5-3.5). Compared to whites, African Americans of low, medium, and high African ancestry had 1.6-, 4.1-, and 5.2-fold increased odds of sero-positivity to H. pylori, primarily related to CagA sero-positive strains, for which increasing African ancestry led to 2.5-, 9.6-, and 13.1-fold increased odds. Among African Americans alone, compared to those of low African ancestry, African Americans of medium and high African ancestry had 2.5- and 3.4-fold increased odds of sero-positivity to H. pylori, and 3.5- and 4.9-fold increased odds of CagA sero-positive H. pylori strains. Conclusions: Host genetic variation and/or lifestyle factors associated with African ancestry contribute to the likelihood of infection with H. pylori, particularly its virulent strains, in this low-income U.S. southern population. Impact: Our findings that low-income African Americans of high African ancestry have a particularly high prevalence of antibodies against H. pylori provides a framework for further research into better detection and prevention of gastric cancer in this population.
    Type of Publication: Journal article published
    PubMed ID: 21357376
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