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  • 1
    Keywords: CANCER ; Germany ; LUNG ; lung cancer ; LUNG-CANCER ; SYSTEM ; CANCER MORTALITY ; COHORT ; cohort studies ; cohort study ; cohort-studies ; DEATH ; DISEASE ; DISEASES ; DNA adducts ; EPIDEMIOLOGY ; EXPOSURE ; HEPATOCELLULAR-CARCINOMA ; HISTORY ; incidence ; iron foundry ; larynx ; liver ; LONG-TERM ; missing death certificates ; MORTALITY ; mouth ; NEW-YORK ; occupation ; PHARYNX ; POPULATION ; PRIMARY LIVER-CANCER ; RISK ; RISKS ; SITE ; SITES ; WORKERS
    Abstract: Background Observations of an increased incidence of cancers of the upper aero-digestive tract (pharynx, esophagus, larynx, lung) among workers of local German foundries gave rise to concern about a potentially elevated occupational risk of those cancer sites. The purpose of the study was to examine whether occupational exposure in iron foundries increases the risk of cancer. Methods A historical cohort study of 17,708 male German production workers in 37 iron foundries who were first employed in 1950-1985 with a minimum employment period of 1 year was initiated. Employment and occupational histories were collected. Mortality was compared with that of the German general population during 1950-1993 using a new method for computing the SMR when not all causes of death are available (called SMR*). Results Mortality from all causes was elevated to SMR = 115.4 (95% confidence interval (CI) = 111.9-119.1), as was for total cancer (SMR* = 123.8, CI = 102.1-152.6), especially cancers of the lung (SMR* = 163.9, CI = 123.9-223.0) and liver (SMR* = 322.5, CI = 149.5-844.8), and diseases of the respiratory system (SMR* = 147.6, CI = 100.4-221.5). Non- significant elevations of mortality were also found for cancers of the mouth and pharynx (SMR* = 153.5, CI = 82.3-359.8) and larynx (SMR* = 173.1, CI = 85.5-550.5). Mortality from various causes of death was higher among workers with shorter exposure periods than among long-term employees. The elevated mortality persisted for years and decades after termination of employment. Conclusions The results provide further evidence for an increased risk of lung cancer and possibly other cancers of the upper aero-digestive tract among foundry workers. Special attention should be paid to the strongly increased mortality from liver cancer and the mortality pattern among employees having terminated work. (C) 2003 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 12594777
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  • 2
    Keywords: CANCER ; SURVIVAL ; Germany ; neoplasms ; DIAGNOSIS ; COHORT ; DISEASE ; DISEASES ; MORTALITY ; POPULATION ; RISK ; RISKS ; PATIENT ; RISK-FACTORS ; BREAST ; LYMPHOMA ; NUMBER ; CLINICAL-TRIALS ; risk factors ; case-control studies ; INHIBITORS ; case-control study ; case control studies ; INTERVAL ; DRUGS ; RISK-FACTOR ; PRAVASTATIN ; PROTEIN GERANYLGERANYLATION
    Abstract: Background: Statins, drugs used to treat dyslipidemia, may have anticancer properties. We have evaluated lymphoma risk associated with regular statin use in an international case-control study. Methods: This case-control study included 2,362 cases of incident B- and T-cell lymphoma from Czech Republic, France, Germany, Ireland, Italy, and Spain and 2,206 hospital or population controls. Information on drug use, diagnosis at admission (for hospital controls), and putative risk factors for lymphoma was collected with personal interviews. Hospital controls admitted for diseases possibly entailing use of statins were excluded from the analysis. Results: The odds ratio for regular statin use was 0.61 (95% confidence interval, 0.45-0.84); all major lymphoma subtypes showed similarly decreased risks. Decreased risks were observed in all centers. Duration of statin use was not associated with a greater reduction in the risk of lymphoma. Use of other lipid lowering drugs, such as fibrates, did not significantly modify the risk of lymphoma (odds ratio, 0.75; 95% confidence interval, 0.44-1.27). Conclusion: Statin use was associated with an important reduction in lymphoma risk, adding to the growing evidence of anticancer properties of this group of drugs. These results are reassuring for the increasing number of patients taking statins on a regular basis
    Type of Publication: Journal article published
    PubMed ID: 16702371
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  • 3
    Keywords: Germany ; occupation ; POPULATION ; RISK-FACTORS ; LYMPHOMA ; UNITED-STATES ; ASBESTOS EXPOSURE ; MULTIPLE-MYELOMA ; NON-HODGKINS-LYMPHOMA ; case control studies ; ELECTRIC UTILITY WORKERS ; MULTICENTER CASE-CONTROL ; MAGNETIC-FIELDS ; ORGANIC-SOLVENTS ; DEATH-CERTIFICATE
    Type of Publication: Journal article published
    PubMed ID: 16361401
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  • 4
    Keywords: Germany ; DIAGNOSIS ; SUPPORT ; EXPOSURE ; HISTORY ; POPULATION ; RISK ; PATIENT ; ASSOCIATION ; CARBON ; LYMPHOMA ; HEALTH ; AGE ; smoking ; REGION ; REGIONS ; SAFETY ; case-control studies ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; FOLLICULAR LYMPHOMA ; AROMATIC-HYDROCARBONS ; case control study ; case-control study ; REGRESSION ; INCREASE ; case control studies ; INTERVAL ; analysis ; methods ; POWER ; female ; Male ; odds ratio ; population-based ; E ; case control ; LOGISTIC-REGRESSION ; POINT ; case-control ; CLICK ; PERSONAL INTERVIEW
    Abstract: To analyze the relationship between exposure to chlorinated and aromatic organic solvents and malignant lymphoma in a multi-centre, population-based case-control study. METHODS: Male and female patients with malignant lymphoma (n = 710) between 18 and 80 years of age were prospectively recruited in six study regions in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/Gütersloh, and Munich). For each newly recruited lymphoma case, a gender, region and age-matched (+/- 1 year of birth) population control was drawn from the population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least one year. On the basis of job task-specific supplementary questionnaires, a trained occupational physician assessed the exposure to chlorinated hydrocarbons (trichloroethylene, tetrachloroethylene, dichloromethane, carbon tetrachloride) and aromatic hydrocarbons (benzene, toluene, xylene, styrene). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking (in pack years) and alcohol consumption. To increase the statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. RESULTS: We observed a statistically significant association between high exposure to chlorinated hydrocarbons and malignant lymphoma (Odds ratio = 2.1; 95% confidence interval 1.1-4.3). In the analysis of lymphoma subentities, a pronounced risk elevation was found for follicular lymphoma and marginal zone lymphoma. When specific substances were considered, the association between trichloroethylene and malignant lymphoma was of borderline statistical significance. Aromatic hydrocarbons were not significantly associated with the lymphoma diagnosis. CONCLUSION: In accordance with the literature, this data point to a potential etiologic role of chlorinated hydrocarbons (particularly trichloroethylene) and malignant lymphoma. Chlorinated hydrocarbons might affect specific lymphoma subentities differentially. Our study does not support a strong association between aromatic hydrocarbons (benzene, toluene, xylene, or styrene) and the diagnosis of a malignant lymphoma.
    Type of Publication: Journal article published
    PubMed ID: 17407545
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  • 5
    Keywords: CANCER ; POPULATION ; RISK ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; FOLLICULAR LYMPHOMA ; TUMORIGENESIS ; NON-HODGKIN-LYMPHOMA ; COMMON VARIANTS ; NECROSIS-FACTOR TNF ; RAL GTPASES
    Abstract: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10-21), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10-10), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10-8) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10-13 and 3.63 x 10-11, respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
    Type of Publication: Journal article published
    PubMed ID: 25261932
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  • 6
    Keywords: POPULATION ; validation ; ASSOCIATION ; TRIAL ; DESIGN ; CIGARETTE-SMOKING ; COMPUTED-TOMOGRAPHY ; TASK-FORCE ; PREDICTION MODELS ; DECISION CURVE ANALYSIS
    Abstract: Lung cancer risk prediction models are considered more accurate than the eligibility criteria based on age and smoking in identification of high-risk individuals for screening. We externally validated four lung cancer risk prediction models (Bach, Spitz, LLP, and PLCOM2012) among 20,700 ever smokers in the EPIC-Germany cohort. High-risk subjects were identified using the eligibility criteria applied in clinical trials (NELSON/LUSI, DLCST, ITALUNG, DANTE, and NLST) and the four risk prediction models. Sensitivity, specificity, and positive predictive value (PPV) were calculated based on the lung cancers diagnosed in the first 5 years of follow-up. Decision curve analysis was performed to compare net benefits. The number of high-risk subjects identified by the eligibility criteria ranged from 3,409 (NELSON/LUSI) to 1,458 (NLST). Among the eligibility criteria, the DLCST produced the highest sensitivity (64.13%), whereas the NLST produced the highest specificity (93.13%) and PPV (2.88%). The PLCOM2012 model showed the best performance in external validation (C-index: 0.81; 95% CI, 0.76-0.86; E/O: 1.03; 95% CI, 0.87-1.23) and the highest sensitivity, specificity, and PPV, but the superiority over the Bach model and the LLP model was modest. All the models but the Spitz model showed greater net benefit over the full range of risk estimates than the eligibility criteria. We concluded that all of the lung cancer risk prediction models apart from the Spitz model have a similar accuracy to identify high-risk individuals for screening, but in general outperform the eligibility criteria used in the screening trials. Cancer Prev Res; 8(9); 777-85. (c)2015 AACR.
    Type of Publication: Journal article published
    PubMed ID: 26076698
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  • 7
    Keywords: CELLS ; EXPRESSION ; BLOOD ; CELL ; THERAPY ; POPULATION ; RISK ; GENE ; PROTEIN ; PROTEINS ; MOLECULES ; LIGAND ; RESPONSES ; DNA ; MECHANISM ; DENDRITIC CELLS ; mechanisms ; T-CELLS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; MOLECULE ; LYMPHOMA ; GRAVES-DISEASE ; WOMEN ; case-control studies ; IMMUNE-RESPONSE ; B-CELL LYMPHOMA ; NON-HODGKINS-LYMPHOMA ; case-control study ; SAN-FRANCISCO ; VARIANT ; INCREASE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; non-Hodgkin lymphoma ; dendritic cell ; single-nucleotide polymorphism ; USA ; population-based ; B-CELL ; FRANCISCO BAY AREA ; non Hodgkin lymphoma ; interactions ; NUCLEOTIDE ; SOLUBLE CD40 LIGAND
    Abstract: CD40 and its ligand, CD154, are major costimulatory molecules whose interactions are important in humoral and cellular immunity. We hypothesized that single nucleotide polymorphisms (SNPs) in TNFRSF5 and TNFSF5 encoding the CD40 and CD154 proteins, respectively, influence lymphoma risk, particularly a functional TNFRSF5 SNP (-1C〉T, rs1883832) associated with reduced B-cell CD40 expression. TNFRSF5 and TNFSF5 SNPs were examined in a population-based case-control study of non-Hodgkin lymphoma (376 cases/801 controls with DNA), and compelling findings were followed up in 2 independent populations. Pooled analyses of all 3 case-control studies (total N = 1776 non-Hodgkin lymphoma cases, N = 2482 controls) revealed an increased risk of follicular lymphoma (FL) associated with the TNFRSF5-1TT genotype (odds ratio = 1.6; 95% confidence interval, 1.1-2.4). In addition, among women, an inverse association was found between the variant A allele for a TNFSF5 6809G〉A SNP and FL risk (OR=.61; 95% Cl, 0.36-0.98). In genotype-phenotype studies, significantly reduced circulating soluble CD40 was observed in TNFRSF5-1TT compared with -1CC carriers. Further, dendritic cells from those with -1TT versus -1CC genotypes exhibited lower CD40 cell surface expression. These results suggest that the TNFRSF5 -1C〉T polymorphism may increase FL susceptibility through mechanisms that hinder cellular immune responses. Further studies are needed to explore these findings
    Type of Publication: Journal article published
    PubMed ID: 18287517
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  • 8
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    Radiologe 50 (8), 654-661 
    Keywords: CANCER ; Germany ; LUNG ; imaging ; lung cancer ; LUNG-CANCER ; DEATH ; EPIDEMIOLOGY ; POPULATION ; RISK ; computed tomography ; AIR-POLLUTION ; early detection ; prevention ; DESIGN ; risk factors ; smoking ; RISK FACTOR ; tomography ; COMPUTED-TOMOGRAPHY ; PROJECT ; FACTOR-I ; FRAMEWORK ; SCREENING TRIAL ; AREA ; ROUTINE ; Multislice computed tomography (MSCT) ; MULTISLICE-CT ; Prevention potential
    Abstract: Lung cancer is by far the most common form of cancer worldwide and in Germany is now "only" still the commonest cause of death from cancer. The most important single risk factor is smoking but in selected population groups, for example in the professional area, other factors can also play a role which cannot be ignored and open up a corresponding potential for prevention. Effective early detection procedures are at present unknown. The most promising, however, is multislice computed tomography (MSCT) which for this reason is presently being tested for effectiveness in several large research projects. The results are not expected for some years. Until then the early detection of lung cancer with MSCT cannot be considered suitable for routine use but can only be justified within the framework of research studies
    Type of Publication: Journal article published
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  • 9
    Keywords: BLOOD ; Germany ; CLASSIFICATION ; DIAGNOSIS ; INFORMATION ; DISEASE ; DISEASES ; EPIDEMIOLOGY ; EXPOSURE ; HISTORY ; occupation ; POPULATION ; RISK ; SAMPLE ; INFECTION ; animals ; LYMPHOMA ; DESIGN ; AGE ; etiology ; leukemia ; UNITED-STATES ; case-control studies ; vaccination ; NON-HODGKINS-LYMPHOMA ; RABBIT ; IMMUNIZATION ; ADULT ; ADULTS ; case control study ; case-control study ; CHILDHOOD ; DIETARY FACTORS ; HAY-FEVER ; HL ; HUMAN T-CELLS ; HYGIENE HYPOTHESIS ; MEDICAL HISTORY ; NHL ; population-based case-control study ; REGISTRY ; REGRESSION ; SAN-FRANCISCO ; SHEEP
    Abstract: A multi-centre, population-based case-control study of lymphoma among adults was conducted in Germany from 1999-2003. The study comprised 700 incident cases (Hodgkin lymphomas and non Hodgkin's lymphoma, NHL) in the age range 18-80 years and 700 age-, sex- and area-matched controls obtained from population registries. Diagnosis was based on the REAL/WHO classification. Information on demographic characteristics, lifestyle, medical history and occupation was obtained by in-person interviews. Each participant was asked for a 24 ml blood sample. First results are focused on basic demographic characteristics, contact to animals, childhood diseases and vaccinations. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The ORs for lymphoma were decreased for exposure to sheep and goats (OR = 0.7; 95% CI = 0.5-0.9), for rabbits and hare (OR = 0.7; 95% CI = 0.5-0.9), measles infection (OR = 0.6; 95% CI = 0.5-0.9), Bordetella pertussis infection (OR = 0.7; 95% CI = 0.6-0.95), and tetanus vaccination (OR = 0.5; 95% CI = 0.3-0.9). Increased risk of lymphoma was associated with exposure to cattle (OR = 1.3; 95% CI = 1.03-1.7) and immunization for tuberculosis (OR = 1.5; 95% CI = 0.997-2.4). The results of this study are partly consistent with the hygiene hypothesis. The inconsistencies of some of the findings with an explanation by the Th1/Th2 paradigm, however, warrant further research and may indicate that broader explanatory concepts are needed. (C) 2004 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15158093
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  • 10
    Keywords: CELL ; LUNG ; COHORT ; cohort studies ; cohort study ; DISEASE ; POPULATION ; RISK ; DISTINCT ; GENE ; GENES ; RISK-FACTORS ; AIR-POLLUTION ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; PHENOTYPES ; PATTERNS ; HEALTH ; risk factors ; REGION ; REGIONS ; PHENOTYPE ; POPULATIONS ; IMMUNE-RESPONSE ; OUTCOMES ; pathology ; PREVALENCE ; TYPE-2 ; ATOPY ; SERUM ; CYTOKINE ; ADULT ; ADULTS ; HAY-FEVER ; REGISTRY ; REGRESSION ; ASSOCIATIONS ; air pollution ; CANDIDATE GENES ; SWITZERLAND ; LEVEL ; analysis ; methods ; T helper cell ; prospective ; CANDIDATE ; RISK-FACTOR ; RELEVANCE ; REGISTRIES ; E ; COMMUNITY ; IGE LEVELS ; CELL RESPONSE
    Abstract: ABSTRACT: BACKGROUND: Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations. METHODS: Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis. RESULTS: We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G〉C) and IL18(-137G〉C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G〉C) polymorphism was also associated with the prevalence of hay fever. CONCLUSION: Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes
    Type of Publication: Journal article published
    PubMed ID: 16759385
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