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  • 1
    Abstract: Grb2-associated binder 1 (Gab1) plays an important role in the regulation of cell growth and transformation. A single nucleotide polymorphism (SNP) (rs3805246) in the Gab1 gene has been suggested to be related to the risk of Helicobacter pylori infection and chronic atrophic gastritis (CAG) in a study from Japan. We aimed to assess the associations in a population-based study from Germany. In the baseline examination of ESTHER, a population-based study conducted in Saarland, serum pepsinogen I and II and H. pylori serostatus were measured by ELISA. The Gab1 SNP (rs3805246) was genotyped in 351 serologically defined CAG cases and 351 age- and sex-matched non-CAG controls. A nonsignificant association was observed between the Gab1 SNP and CAG, with an adjusted odds ratio of 1.15 (0.85-1.55) for AA/AG carriers compared to GG carriers. The magnitude of the association did not change when the analysis was restricted to H. pylori seropositive subjects. Furthermore, no significant relation was found between the SNP and H. pylori seropositivity among non-CAG controls. We could not confirm a major association between Gab1 SNP (rs3805246) and the predisposition to H. pylori infection and CAG in this study population from Germany. Further studies with larger sample size are needed to clarify a potential modest effect of Gab1 genetic polymorphisms.
    Type of Publication: Journal article published
    PubMed ID: 20602450
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  • 2
    Keywords: CANCER ; Germany ; DIAGNOSIS ; COHORT ; cohort studies ; cohort study ; EPIDEMIOLOGY ; POPULATION ; RISK ; INFECTION ; SERA ; IMPACT ; RISK-FACTORS ; ASSOCIATION ; antibodies ; antibody ; AGE ; WOMEN ; MEN ; risk factors ; RATES ; cancer risk ; PREVALENCE ; GASTRIC-CANCER ; HELICOBACTER-PYLORI ; HETEROGENEITY ; SERUM ; ELISA ; ONCOLOGY ; ASSOCIATIONS ; POPULATION-BASED COHORT ; RE ; gastric cancer ; HELICOBACTER-PYLORI INFECTION ; USA ; JAPANESE ; odds ratio ; RISK-FACTOR ; population-based ; PRECURSOR ; Helicobacter pylori ; OLDER-ADULTS ; SERUM PEPSINOGEN-I ; CAGA ; chronic atrophic gastritis ; gastric ; pepsinogen ; SERUM PEPSINOGENS
    Abstract: Chronic atrophic gastritis (CAG), a precursor of intestinal gastric cancer, is mostly ascertained noninvasively by serum pepsinogens in epidemiologic studies. However, serological definitions vary widely. We aimed to investigate the impact of this variation on estimated prevalence of CAG and its association with its main risk factors, age and Helicobacter pylori infection. Serum pepsinogen I and II and antibodies against H. pylori were measured by ELISA among 9,444 women and men aged 50-74 years in a population-based cohort study in Saarland/Germany. Application of the various definitions resulted in a wide range of prevalence estimates of CAG prevalence (2.1%-8.2%, with an outlier of 18.8% for one particular definition) and its associations with age and H. pylori infection (age adjusted odds ratios, OR, for CagA positive H. pylori infection: 0.98-4.48). Definitions of CAG based on both pepsinogen I and the pepsinogen I/II ratio or on the pepsinogen I/II ratio only revealed much clearer associations with both age and H. pylori infection than definitions of CAG based on pepsinogen I only (ORs for H. pylori infection: 1.45-4.48 and 0.86-1.30, respectively). Epidemiologic findings on CAG lack comparability due to the heterogeneity in serologic definitions of CAG. The association of age and H. pylori infection with CAG may be strongly underestimated in studies in which CAG is defined by pepsinogen I only. (c) 2007 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 17691112
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  • 3
    Keywords: CANCER ; Germany ; EPIDEMIOLOGY ; POPULATION ; GENDER DIFFERENCES ; AGE ; RATES ; DATABASE ; HIGH-RISK ; Jun ; PREVALENCE ; GASTRIC-CANCER ; STOMACH-CANCER ; PRECANCEROUS LESIONS ; SERUM ; ADULTS ; RE ; INCREASE ; LEVEL ; HELICOBACTER-PYLORI INFECTION ; GENDER ; SERUM-LEVELS ; intestinal metaplasia ; PERNICIOUS-ANEMIA ; NONINVASIVE MEASUREMENT ; DUODENAL-ULCER ; RURAL-POPULATION ; SERUM PEPSINOGEN-I ; SYDNEY SYSTEM
    Abstract: Chronic atrophic gastritis (CAG) is a well-established precursor of intestinal gastric cancer, but epidemiologic data about its occurrence are sparse. We provide an overview on studies that examined the prevalence of CAG in different parts of the world. Articles containing data about the prevalence of chronic atrophic gastritis in unselected population samples and published until November 2005 were identified by searching the MEDLINE database. Furthermore, the references in the identified publications were screened for additional suitable studies. Studies comprising at least 50 subjects were included. Forty-one studies providing data on the prevalence of CAG in unselected population samples could be identified. CAG was determined by gastroscopy in 15 studies and by pepsinogen serum levels in 26 studies. Although results are difficult to compare due to the various definitions of CAG used, a strong increase with age, the lack of major gender differences, and strong variations between populations and population groups (in particular, relatively high rates in certain Asian populations) could be observed quite consistently. We conclude that CAG is relatively common among older adults in different parts of the world, but large variations exist. Large-scale international comparative studies with standardized methodology to determine CAG are needed to provide a coherent picture of the epidemiology of CAG in various populations. Noninvasive measurements of CAG by pepsinogen levels may be particularly suited for that purpose
    Type of Publication: Journal article published
    PubMed ID: 16775164
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  • 4
    Keywords: CANCER ; carcinoma ; Germany ; EPIDEMIOLOGY ; POPULATION ; RISK ; IMPACT ; CARCINOGENESIS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; VARIANTS ; PROMOTER ; SNP ; GENOTYPES ; GASTRIC-CANCER ; CYTOKINE ; ADULT ; ADULTS ; VARIANT ; SINGLE NUCLEOTIDE POLYMORPHISMS ; CHINESE ; development ; HELICOBACTER-PYLORI INFECTION ; GENOTYPE ; HAPLOTYPES ; INTERLEUKIN-10 ; chronic atrophic gastritis ; OLDER ; Pro-inflammatory
    Abstract: Background: Pro-inflammatory polymorphisms have been suggested to explain part of the individual diversity in susceptibility to gastric carcinogenesis. We aimed to assess their impact on the risk of chronic atrophic gastritis (CAG) in a population-based study. Methods: Among 9953 older adults from Saarland/Germany, eight single nucleotide polymorphisms (SNPs) were assessed for 534 cases with serologically defined CAG and 534 age- and sex-matched controls at baseline examination. Results: Of the 8 SNPs, only IL10 T-819C showed a borderline significant association with CAG risk (odds ratio for CC versus TT: 1.67 (95% confidence interval: 1.01-2.76)). No significant differences were observed for the distribution of inferred haplotypes between cases and controls. However, joint evaluation of several cytokine variants suggested an increased risk of CAG among individuals carrying several pro-inflammatory genotypes. Conclusions: Our findings suggest that a pro-inflammatory genetic profile may contribute to inter-individual variation in gastric cancer risk by increasing the susceptibility to the development of CAG. (C) 2008 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19013788
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  • 5
    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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  • 6
    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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  • 7
    Keywords: CANCER ; EXPRESSION ; carcinoma ; MODEL ; RISK ; GENE ; GENETIC POLYMORPHISMS ; ASSOCIATION ; polymorphism ; adenocarcinoma ; STOMACH-CANCER ; HELICOBACTER-PYLORI INFECTION ; INCREASED RISK ; ESOPHAGEAL CANCER ; OLDER-ADULTS ; stomach cancer ; chronic atrophic gastritis ; CANCER GENETICS ; GLEASON SCORE ; LY-6 FAMILY
    Abstract: BACKGROUND & AIMS: An association between gastric cancer and the rs2294008 (C 〉 T) polymorphism in the prostate stem cell antigen (PSCA) gene has been reported for several Asian populations. We set out to determine whether such an association exists in white individuals. METHODS: We genotyped 166 relatives of gastric cancer patients, including 43 Helicobacter pylori-infected subjects with hypochlorhydria and gastric atrophy, 65 infected subjects without these abnormalities, 58 H pylori-negative relatives, and 100 population controls. Additionally, a population-based study of chronic atrophic gastritis provided 533 cases and 1054 controls. We then genotyped 2 population-based, case-control studies of upper gastrointestinal cancer: the first included 312 gastric cancer cases and 383 controls; the second included 309 gastric cancer cases, 159 esophageal cancer cases, and 211 controls. Odds ratios were computed from logistic models and adjusted for confounding variables. RESULTS: Carriage of the risk allele (T) of rs2294008 in PSCA was associated with chronic atrophic gastritis (adjusted odds ratio [OR], 1.5; 95% confidence interval [CI]: 1.1-1.9) and noncardia gastric cancer (OR, 1.9; 95% CI: 1.3-2.8). The association was strongest for the diffuse histologic type (OR, 3.2; 95% CI: 1.2-10.7). An inverse association was observed between carriage of the risk allele and gastric cardia cancer (OR, 0.5; 95% CI: 0.3-0.9), esophageal adenocarcinoma (OR, 0.5; 95% CI: 0.3-0.9), and esophageal squamous cell carcinoma (OR, 0.4; 95% CI: 0.2-0.9). CONCLUSIONS: The rs2294008 polymorphism in PSCA increases the risk of noncardia gastric cancer and its precursors in white individuals but protects against proximal cancers
    Type of Publication: Journal article published
    PubMed ID: 21070776
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  • 8
    Keywords: RISK ; INFECTION ; microbiology ; ENGLAND ; chronic atrophic gastritis
    Type of Publication: Meeting abstract published
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  • 9
    Keywords: USA ; chronic atrophic gastritis ; antibody ; antibodies ; ASSOCIATION ; SERUM ; PROTEIN ; PROTEINS
    Type of Publication: Meeting abstract published
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  • 10
    Keywords: PROTEINS ; PROTEIN ; RISK ; INFECTION ; CANCER ; evaluation ; GASTRIC-CANCER ; cancer risk ; USA ; CANCER-RISK
    Type of Publication: Meeting abstract published
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