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  • DKFZ Publication Database  (3)
  • ANTIGENS  (3)
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  • DKFZ Publication Database  (3)
  • 1
    Keywords: ANTIGENS ; PREVALENCE ; METAANALYSIS ; SERUM ANTIBODIES ; multiplex serology ; CYTOTOXIN
    Abstract: Gastric cancer is a rare outcome of chronic Helicobacter pylori infection. Serologic profiles may reveal bacterial, environmental and/or host factors associated with cancer risk. We therefore compared specific anti-H. pylori antibodies among populations with at least twofold differences in gastric cancer mortality from Mexico, Colombia and Chile. Our study included 1,776 adults (mean age 42 years) from three nationally representative surveys, equally divided between residents of high- and low-risk areas. Antibodies to 15 immunogenic H. pylori antigens were measured by fluorescent bead-based multiplex assays; results were summarized to identify overall H. pylori seropositivity. We used logistic regression to model associations between antibody seroreactivity and regional cancer risk (high vs. low), adjusting for country, age and sex. Both risk areas had similar H. pylori seroprevalence. Residents in high- and low-risk areas were seroreactive to a similar number of antigens (means 8.2 vs. 7.9, respectively; adjusted odds ratio, OR: 1.02, p = 0.05). Seroreactivities to Catalase and the known virulence proteins CagA and VacA were each significantly (p 〈 0.05) associated with residence in high-risk areas, but ORs were moderate (1.26, 1.42 and 1.41, respectively) and their discriminatory power was low (area under the curve 〈 0.6). The association of Catalase was independent from effects of either CagA or VacA. Sensitivity analyses for antibody associations restricted to H. pylori-seropositive individuals generally replicated significant associations. Our findings suggest that humoral responses to H. pylori are insufficient to distinguish high and low gastric cancer risk in Latin America. Factors determining population variation of gastric cancer burden remain to be identified.
    Type of Publication: Journal article published
    PubMed ID: 26178251
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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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