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  • 1
    Keywords: CANCER ; POPULATION ; RISK ; PROTEIN ; INFECTION ; ASSOCIATION ; antibodies ; PLASMA ; PREVALENCE ; GASTRIC-CANCER ; RANDOMIZED-TRIAL ; FOOD FREQUENCY QUESTIONNAIRE ; ABSORPTION ; ALPHA-TOCOPHEROL ; SUPPLEMENTATION ; SOUTHERN COMMUNITY COHORT ; CAROTENE CONCENTRATIONS
    Abstract: High prevalence of Helicobacter pylori (H. pylori), the leading cause of gastric cancer, and low levels of micronutrients have been observed in many developing countries, and the question remains as to the whether an association between the 2 exists. The present study seeks to further our understanding of this potential connection in the Southern Community Cohort Study, representing a low-income population in the United States. Blood levels of antibodies to H. pylori proteins were assessed by multiplex serology for a sample of 310 African American and white participants, ages 40 to 79 years. Blood collected at baseline was also assayed for levels of carotenoids, tocopherols, retinol, and folate. Multivariate linear regression was used to calculate least-squares mean micronutrient levels within groups defined by H. pylori status. The mean serum levels of all micronutrients assayed were lower among H. pylori+ individuals than H. pylori- individuals, significantly for beta-carotene, folate, and retinol (decreases of 27.6%, 18.6%, and 9.7%, respectively). Individuals who were seropositive to the virulent CagA+ H. pylori strains had even lower mean levels of micronutrients, particularly beta-carotene, folate, total carotenoids, and retinol (decreases of 38.9%, 19.1%, 17.0%, and 11.7%, respectively, compared with H. pylori- individuals). However, dietary micronutrient levels as derived from a food frequency questionnaire did not vary between groups defined by H. pylori status. These results provide support for the hypothesis that H. pylori infection impairs nutrient absorption and suggest a need for future studies to explore the role of H. pylori infection on nutrition and gastric cancer risk in this high-risk population.
    Type of Publication: Journal article published
    PubMed ID: 21436385
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  • 2
    Keywords: POPULATION ; INFECTION ; BIOMARKERS ; HEALTH ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; HELICOBACTER-PYLORI ; METAANALYSIS ; INTERLEUKIN-8 ; serology ; CHINESE MEN
    Abstract: PURPOSE: Chronic inflammation has been hypothesized to play a significant role in the aetiology of cancer, including gastric cancer. In the present study, we sought to examine pre-diagnostic systemic cytokine levels in plasma, which can be seen as markers of aggregate inflammation, and risk of distal gastric cancer in a case-control study nested within the prospective Shanghai Men's Health Study. METHODS: Circulating levels of eight inflammation-related cytokines were measured in the plasma collected at baseline for 180 incident cases of distal gastric cancer and 358 matched controls. Helicobacter pylori sero-positivity was assessed using multiplex serology. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CI). RESULTS: Individuals with IL-8 levels above the lowest quartile were at twofold increased odds of gastric cancer [OR 1.91 (95 % CI 1.05-3.46), OR 2.10 (95 % CI 1.19-3.74), and OR 2.30 (95 % CI 1.26-4.19), for the second through fourth quartiles, respectively]. While there were suggestions of an increase in risk with increased level of many of the other cytokines measured (IL-1beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma), no significant associations were found at the p 〈 0.05 level. Infection with CagA-positive H. pylori did not modify these associations. CONCLUSIONS: In a population with high gastric cancer incidence and high H. pylori prevalence, increased circulating levels of IL-8 may indicate increased risk of gastric cancer. These findings add to our understanding of the disease and further efforts to uncover biomarkers of disease risk.
    Type of Publication: Journal article published
    PubMed ID: 24052422
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  • 3
    Keywords: POPULATION ; INFECTION ; HUMAN-PAPILLOMAVIRUS ; GASTRIC-CANCER ; SERUM ANTIBODIES ; CAGA ; VACUOLATING CYTOTOXIN ; VACA ; GASTRODUODENAL DISEASES ; MONGOLIAN GERBILS
    Abstract: Background: There is biologic plausibility as to why infection with Helicobacter pylori, the leading cause of gastric cancer, may also increase the risk of colorectal cancer, but the epidemiologic findings have been inconsistent. We assessed the association of H. pylori protein-specific infection and colorectal cancer risk in the prospective cohort, the Southern Community Cohort Study. Methods: Multiplex serology was used to measure antibodies to 15 H. pylori proteins in prediagnostic blood among 188 incident colorectal cancer cases and 370 controls matched by age, race, sex, and blood collection timing. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). Results: Overall H. pylori prevalence was not associated with colorectal cancer risk (OR, 1.03; 95% CI, 0.59-1.77). However, seropositivity to any of five specific H. pylori proteins (VacA, HP231, HP305, NapA, and HcpC) was associated with a significant 60% to 80% increase in odds of risk. These associations became even stronger when limited to colon cancer risk, particularly for the known H. pylori toxin VacA (OR, 2.24; 95% CI, 1.22-4.11), including a significant, positive dose-response association by VacA antibody levels in quartiles (P 〈 0.05). Associations with VacA seropositivity were especially strong for early-onset and late-stage cancers. Conclusions: The findings raise the hypothesis that individuals with high levels of antibodies to specific H. pylori proteins may be at higher risk of colon cancer. Impact: Further investigation of the H. pylori-colorectal cancer association is warranted to determine the possibility of protein-specific antibody levels as a risk biomarker.
    Type of Publication: Journal article published
    PubMed ID: 24045925
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  • 4
    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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  • 5
    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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