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  • DKFZ Publication Database  (6)
  • multiplex serology  (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: INFECTION ; ASSOCIATION ; multiplex serology
    Abstract: Helicobacter pylori (H. pylori) seropositivity has been inconsistently associated with pancreatic cancer. We, therefore, investigated the association between H. pylori seropositivity and pancreatic cancer in a case-control study nested within Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of Finnish male smokers. Pancreatic cancer cases (n = 353) and control subjects (n = 353) were matched on date of baseline serum collection, age at randomization, and follow-up time (up to 23.9 years). We used a multiplex serology assay to determine the sero-status of antibodies against 15 H. pylori-specific antigens in fasting serum samples. Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Neither targeted H. pylori antigens in serum nor the combination of all was associated with development of pancreatic cancer (combination of all: OR, 0.85; 95% CI, 0.49-1.49). Our results suggest that H. pylori is not a risk factor for pancreatic cancer.
    Type of Publication: Journal article published
    PubMed ID: 24089457
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  • 3
    Keywords: FOLLOW-UP ; EPIDEMIOLOGY ; PROTEINS ; INFECTION ; cancer risk ; glutathione-S-transferase ; multiplex serology ; FOOD-CONSUMPTION HABITS ; EARLY-CHILDHOOD ; GASTRIC EPITHELIAL-CELLS
    Abstract: BACKGROUND: Helicobacter pylori infection that is usually acquired in childhood and lasts for lifetime is mostly asymptomatic but associated with severe gastrointestinal disease including cancer. During chronic infection, the gastric mucosa is histologically changing. This forces H. pylori to permanent adaptation in its gastric habitat by expression of different proteins which might be reflected in distinctive antibody patterns. METHODS: To characterize dynamics of the immune response to H. pylori we analysed 1797 sera of a cross-sectional study representative for the German population (age range 1-82 years) with multiplex serology, a fluorescent bead-based antibody binding assay that allows simultaneous and quantitative detection of antibodies. Fifteen recombinant, affinity-purified H. pylori proteins (UreA, GroEL, Catalase, NapA, CagA, CagM, Cagdelta, HP0231, VacA, HpaA, Cad, HyuA, Omp, HcpC and HP0305) were used as antigens. RESULTS: H. pylori seroprevalence (positivity for at least three antigens) was 48% and increased with age from 12% in children 〈15 years to 69% in females and 90% in males 〉65 years. Prevalences were highest (〉83%) for Omp, VacA and GroEL. For 11 proteins, seroprevalence was higher in males than females (P 〈 0.05) from age 55 onwards. For all antigens, the median prevalence increase per age decade was stronger in males (8.4%, range 3.8-12.9%) than females (6.1%, range 3.4-10.8%). However, among seropositives the median number of antigens recognized increased from children 〈15 years to individuals 〉65 years stronger in females (P = 0.02). Antibody reactivities to GroEL, HyuA, CagM, Catalase, NapA and UreA also increased stronger in females (average 1.7-fold/decade, SD 0.5) than in males (1.5-fold/decade, SD 0.4). CONCLUSION: H. pylori antibody response accumulates qualitatively and quantitatively with age. This may reflect a lifelong stimulation of the immune response by chronically active infection.
    Type of Publication: Journal article published
    PubMed ID: 24782915
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  • 4
    Keywords: PROTEINS ; INFECTION ; ASSOCIATION ; multiplex serology ; GENERAL-POPULATION ; ESOPHAGEAL ; SEROPOSITIVITY ; ATROPHIC GASTRITIS ; China ; LINXIAN
    Abstract: Helicobacter pylori (H. pylori) infection is the strongest known risk factor for gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of noncardia gastric cancer in Linxian, China. We included 448 GNCA cases and 1242 controls from two time points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to 〉/=4 of the 15 included antigens. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk factors. In addition, we undertook a meta-analysis combining H. pylori multiplex serology data from both time points. H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both time points in a meta-analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA. We identified six individual antigens that confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen that may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA.
    Type of Publication: Journal article published
    PubMed ID: 25845708
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  • 5
    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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  • 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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