Radon is a risk factor for lung cancer and uranium miners are more exposed than the general population. A genome-wide interaction analysis was carried out to identify genomic loci, genes or gene sets that modify the susceptibility to lung... more
Radon is a risk factor for lung cancer and uranium miners are more exposed than the general population. A genome-wide interaction analysis was carried out to identify genomic loci, genes or gene sets that modify the susceptibility to lung cancer given occupational exposure to the radioactive gas radon. Samples from 28 studies provided by the International Lung Cancer Consortium were pooled with samples of former uranium miners collected by the German Federal Office of Radiation Protection. In total, 15,077 cases and 13,522 controls, all of European ancestries, comprising 463 uranium miners were compared. The DNA of all participants was genotyped with the OncoArray. We fitted single-marker and in multi-marker models and performed an exploratory gene-set analysis to detect cumulative enrichment of significance in sets of genes. We discovered a genome-wide significant interaction of the marker rs12440014 within the gene CHRNB4 (OR = 0.26, 95% CI 0.11-0.60, p = 0.0386 corrected for mult...
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Research Interests: Endocrinology, Chemistry, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Medicine, and 14 moreNeurotoxicology, Striatum, Glutamate, Internal Medicine, PMC, Ferritin, White matter, Globus Pallidus, Parkinson, Neurosciences, Haemochromatosis, Glutamate Receptor, Pharmacology and pharmaceutical sciences, and Welders
Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has... more
Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin. For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performan...
Research Interests: Australia, Surgical Oncology, Medicine, Germany, Humans, and 11 moreAsbestos, Male, Mesothelioma, Aged, Middle Aged, Biomarker, Adult, Calretinin, Calbindin, DDC, and lung neoplasms
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Occupational exposure to manganese (Mn) has been associated with impairments in olfaction and motor functions, but it has yet to be determined if such effects persist upon cessation of exposure. The objective of this study was to evaluate... more
Occupational exposure to manganese (Mn) has been associated with impairments in olfaction and motor functions, but it has yet to be determined if such effects persist upon cessation of exposure. The objective of this study was to evaluate the influence of former occupational Mn exposure on olfaction within the framework of a prospective cohort study among an elderly German population. Information on job tasks with recognized Mn exposure and data on odor identification assessed with Sniffin' sticks was collected during the second follow-up of the Heinz Nixdorf Recall Study. The study population consisted of 1385 men aged 55-86 years, 354 of whom ever worked in jobs with potential Mn exposure (median 58.3μg/m(3) years, interquartile range 19.0-185μg/m(3) years). Multiple exposure measures, including job tasks, cumulative Mn exposure, and Mn determined in blood samples (MnB) archived at baseline, were used to estimate effects of Mn on olfaction. Having ever worked as welder was ass...
Research Interests: Nonparametric Statistics, Aging, Medicine, Manganese, Neurotoxicology, and 15 moreOlfaction, Population, Humans, Liver, Male, Iron, Aged, Middle Aged, Occupational Exposure, Community Health Planning, Neurosciences, Cohort Studies, Odorants, Pharmacology and pharmaceutical sciences, and Olfaction disorders
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Iron is the major metal found in welding fumes, and although it is an essential trace element, its overload causes toxicity due to Fenton reactions. To avoid oxidative damage, excess iron is bound to ferritin, and as a result, serum... more
Iron is the major metal found in welding fumes, and although it is an essential trace element, its overload causes toxicity due to Fenton reactions. To avoid oxidative damage, excess iron is bound to ferritin, and as a result, serum ferritin (SF) is a recognized biomarker for iron stores, with high concentrations linked to inflammation and potentially also cancer. However, little is known about iron overload in welders. Within this study, we assessed the iron status and quantitative associations between airborne iron, body iron stores, and iron homeostasis in 192 welders not wearing dust masks. Welders were equipped with personal samplers in order to determine the levels of respirable iron in the breathing zone during a working shift. SF, prohepcidin and other markers of iron status were determined in blood samples collected after shift. The impact of iron exposure and other factors on SF and prohepcidin were estimated using multiple regression models. Our results indicate that resp...
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Siderosis due to excessive iron exposure is a rare disease in welders. Less is known about the effect of inhaled iron on systemic iron status in welders. Here we present the association between exposure to iron as major constituent of the... more
Siderosis due to excessive iron exposure is a rare disease in welders. Less is known about the effect of inhaled iron on systemic iron status in welders. Here we present the association between exposure to iron as major constituent of the welding fume and the iron status in German welders. In this analysis we included 192 welders from the German WELDOX study not wearing respirators. Respirable welding fume was measured during one shift and analysed for its metal content. Iron status was assessed with different measures, including serum iron, serum ferritin (SF), transferrin, and prohepcidin. High iron stores were classified according to international standards. The influence of exposure to iron and other factors on the iron status was analysed with multiple regression models. Median shift exposure to respirable iron was 88 µg/m³ (interquartile range 13-690 µg/m³). For the overall study population the prevalence of high iron stores (SF > 200 µg/L) was 31.3%. A lower prevalence was...
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To assess level and trend of exposure to hexavalent chromium (Cr(VI)) in chromium-exposed occupations for the estimation of lung cancer risks in community-based studies. This analysis was based on 3666 personal measurements and auxiliary... more
To assess level and trend of exposure to hexavalent chromium (Cr(VI)) in chromium-exposed occupations for the estimation of lung cancer risks in community-based studies. This analysis was based on 3666 personal measurements and auxiliary data compiled in the German MEGA database from 1988-2009. Cr(VI) was determined spectrophotometrically at 540 nm after reaction with diphenylcarbazide. We assigned jobs tasks with known Cr(VI) exposure using coded and textual information about the workplaces. Measurements below the limit of quantification (LOQ) were multiply imputed according to their distribution above LOQ. Statistical modelling was performed to the log-transformed Cr(VI) concentrations to adjust for duration and reason of sampling. Cr(VI) exposure could be assessed for eight out of 30 jobs tasks with known Cr(VI) exposure. The majority of measurements (53%) were collected in welders (N = 1930), which we further detailed by welding technique. Spray painting and the welding of stain...
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Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies reported an excess of lung cancer among these workers. We examined lung cancer risk among bricklayers within SYNERGY, a... more
Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies reported an excess of lung cancer among these workers. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case-control studies on lung cancer and the joint effects of occupational carcinogens (http://SYNERGY.iarc.fr). The pooled dataset included 15 608 cases and 18 531 controls from 22 centres in Europe, Canada, Hong Kong, and New Zealand. For men ever employed as bricklayers we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for study centre, age, lifetime cigarette smoking history, and employment in occupations with exposures to known or suspected lung carcinogens. We found 1322 cases and 1004 controls who had ever worked as bricklayers (OR: 1.35; 95% CI: 1.22-1.49). There was a clear positive trend with length of employment (P < 0.0001). The relative risk was higher for squamous (OR: 1.4...
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For the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low... more
For the detection of malignant mesothelioma no single biomarker with reasonable sensitivity and specificity has been described so far. Mesothelin, the most prominent blood-based biomarker, is characterized by high specificity but low sensitivity. It might be reasonable to combine biomarkers of different molecular classes in order to improve the overall performance. The aim of this study was to assess the performance of the combination of mesothelin and miR-103a-3p as blood-based biomarker for mesothelioma. Mesothelin concentration in plasma and miR-103a-3p levels in the cellular blood fraction were analyzed in 43 male mesothelioma patients and 52 male controls formerly exposed to asbestos. For the discrimination of epithelioid and biphasic mesothelioma from asbestos-exposed controls mesothelin and miR-103a-3p showed 74% and 89% sensitivity and 85% and 63% specificity, respectively. For the combination of mesothelin and miR-103a-3p a sensitivity of 95% and a specificity of 81% were c...
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Research Interests: Environmental Science, Epidemiology, Environmental Monitoring, Medicine, Exposure Assessment, and 15 moreEnvironmental Sciences, Humans, Best practice, Carcinogens, Historical Data, Exposure, CHEMICAL SCIENCES, Dose Response Relationship, Dust, Epidemiologic Studies, Environmental Exposure, Cumulant, Medical and Health Sciences, lung neoplasms, and Epidemiological monitoring
Research Interests: Materials Science, Environmental Monitoring, Medicine, Germany, Environmental Sciences, and 15 moreHumans, Welding, Young Adult, Chromium, Nickel, Exposure, CHEMICAL SCIENCES, Middle Aged, Adult, Occupational Exposure, Public health systems and services research, Biological Monitoring, Cross Sectional Studies, Medical and Health Sciences, and Respiratory Protective Devices
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Research Interests: Cancer, Environmental Health, Medicine, Logistic Regression, Lung Cancer, and 11 moreInternal Medicine, Risk Factor, Cigarette Smoking, Public health systems and services research, Odds ratio, Case Control Study, Confidence Interval, Adenocarcinoma, Gesundheitswesen, Risk estimation, and Cigarette Smoke
Background: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case–control studies and was... more
Background: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case–control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition.Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA fr...
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In regulatory toxicology, the dose-response relationship between occupational exposure and biomarkers is of importance in setting threshold values. We analyzed the relationships between occupational exposure to polycyclic aromatic... more
In regulatory toxicology, the dose-response relationship between occupational exposure and biomarkers is of importance in setting threshold values. We analyzed the relationships between occupational exposure to polycyclic aromatic hydrocarbons (PAH) and various biomarkers of internal exposure and DNA damage with data from 284 highly exposed male workers. Personal exposure to phenanthrene and other PAHs was measured during shift and correlated with the sum of 1−, 2+9−, 3−, and 4-hydroxyphenanthrenes in post-shift urine. PAHs and hydroxyphenanthrenes were associated with DNA damage assessed in WBC as 8-oxo-7,8-dihydro-2′-deoxyguanosine/106 dGuo and strand breaks by Comet assay as Olive tail moment. Hydroxyphenanthrenes correlated with phenanthrene (Spearman rs = 0.70; P < 0.0001). No correlations could be found between strand breaks and exposure (rs = 0.01, P < 0.0001 for PAHs; rs = −0.03, P = 0.68 for hydroxyphenanthrenes). Correlations with 8-oxo-7,8-dihydro-2′-deoxyguanosine/...
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Research Interests: Endocrinology, Polymorphism, Breast Cancer, Biology, Medicine, and 15 moreLogistic Regression, Humans, Internal Medicine, Breast Cancer Early Detecion and Treatment, Haplotypes, Female, Middle Aged, Genotype, Hormone Therapy, Genetic Variability, Case Control Studies, Risk estimation, Breast Neoplasms, reverse transcriptase polymerase chain reaction, and Genetic predisposition to disease
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Research Interests: Engineering, Chemistry, Archives, Environmental Monitoring, Environmental Chemistry, and 15 moreRisk assessment, Medicine, Statistical Modelling, Aerosols, Humans, Male, Polycyclic Aromatic Hydrocarbon, HYDROCARBONS, Occupational Exposure, Biological markers, Risk Assessment, Metabolite, General Population, Volatilization, and Pharmacology and pharmaceutical sciences
Research Interests: Chemistry, Archives, Environmental Chemistry, DNA damage, Medicine, and 15 moreMultidisciplinary, DNA, Germany, Air Sampling, Humans, Industry, Biomonitoring, Middle Aged, Adult, Occupational Exposure, Biological markers, Biological Monitoring, Coke, Metabolite, and Pharmacology and pharmaceutical sciences
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Research Interests:
The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos,... more
The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons (by its proxy benzo(a)pyrene (BaP)) and respirable crystalline silica). A quantitative job-exposure matrix (JEM) was developed based on statistical modeling of large quantities of personal measurements. Empirical linear models were developed using personal occupational exposure measurements (n = 102306) from Europe and Canada, as well as auxiliary information like job (industry), year of sampling, region, an a priori exposure rating of each job (none, low, and high exposed), sampling and analytical methods, and sampling duration. The model outcomes were used to create a JEM with a quantitative estimate of the level of exposure by job, year, and region. Decreasing time trends were observed for all ...
Research Interests: Environmental Science, Medicine, Exposure Assessment, Canada, Humans, and 12 moreAsbestos, Europe, Journal Article, Chromium, Carcinogens, Nickel, Occupational Exposure, Public health systems and services research, Polycyclic Aromatic Hydrocarbons, Silicon Dioxide, Asbestos Exposure, and lung neoplasms
An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from... more
An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood sa...