Publications by authors named "Heinz-Erich Wichmann"

74 Publications

Application of two job indices for general occupational demands in a pooled analysis of case-control studies on lung cancer.

Scand J Work Environ Health 2021 Sep 3;47(6):475-481. Epub 2021 May 3.

Jan Hovanec, IPA, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.

Objectives: We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer.

Methods: In 13 case-control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands - each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman's Standard International Occupational Prestige Scale) were affected by adjustment for the job indices.

Results: In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56-1.93), PSI 1.33 (95% CI 1.17-1.51)] and women [PHI 1.62 (95% CI 1.24-2.11), PSI 1.31 (95% CI 1.09-1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32-1.58) to 1.30 (95% CI 1.17-1.45)], but not PSI.

Conclusions: Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.
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http://dx.doi.org/10.5271/sjweh.3967DOI Listing
September 2021

Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium.

Occup Environ Med 2021 04 28;78(4):269-278. Epub 2020 Oct 28.

Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, USA.

Objectives: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project.

Methods: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens.

Results: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0).

Conclusions: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.
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http://dx.doi.org/10.1136/oemed-2020-106770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958079PMC
April 2021

Diesel Engine Exhaust Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Exposure-Response Analysis of 14 Case-Control Studies.

Am J Respir Crit Care Med 2020 08;202(3):402-411

Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and ll Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte (CPO-Piemonte), Torino, Italy.

Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes. We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations. We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men. Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 μg/m were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined. We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.
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http://dx.doi.org/10.1164/rccm.201911-2101OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465091PMC
August 2020

Respirable Crystalline Silica Exposure, Smoking, and Lung Cancer Subtype Risks. A Pooled Analysis of Case-Control Studies.

Am J Respir Crit Care Med 2020 08;202(3):412-421

The M. Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype. We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks. Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed. Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated ( trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated ( trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes. Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.
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http://dx.doi.org/10.1164/rccm.201910-1926OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465090PMC
August 2020

[Occurrence of bronchial asthma and age at initial asthma diagnosis-first results of the German National Cohort].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Apr;63(4):397-403

Abteilung Epidemiologie von Krebserkrankungen, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland.

Background: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA.

Material And Methods: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex.

Results: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated.

Conclusion: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time.
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http://dx.doi.org/10.1007/s00103-020-03105-yDOI Listing
April 2020

Exposure to Welding Fumes, Hexavalent Chromium, or Nickel and Risk of Lung Cancer.

Am J Epidemiol 2019 11;188(11):1984-1993

To investigate the risk of lung cancer after exposure to welding fumes, hexavalent chromium (Cr(VI)), and nickel, we analyzed 3,418 lung cancer cases and 3,488 controls among men from 2 German case-control studies (1988-1996). We developed a welding-process exposure matrix from measurements of these agents, and this was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals conditional on study, and they adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welders. Odds ratios for lung cancer with high exposure were 1.55 (95% confidence interval (CI): 1.17, 2.05; median, 1.8 mg/m3 × years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 μg/m3 × years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 μg/m3 × years) for nickel. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration for Cr(VI) and nickel. Our results showed that welding fumes, Cr(VI), and nickel might contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging.
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http://dx.doi.org/10.1093/aje/kwz187DOI Listing
November 2019

Lung cancer and socioeconomic status in a pooled analysis of case-control studies.

PLoS One 2018 20;13(2):e0192999. Epub 2018 Feb 20.

National Institute of Public Health, Bucharest, Romania.

Background: An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study.

Methods: Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens.

Results: The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)).

Conclusion: SES remained a risk factor for lung cancer after adjustment for smoking behavior.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192999PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819792PMC
April 2018

Epidemiology in Germany-general development and personal experience.

Eur J Epidemiol 2017 08 16;32(8):635-656. Epub 2017 Aug 16.

Institute of Epidemiology, 2, Helmholtz Center Munich, Munich, Germany.

Did you ever hear about epidemiology in Germany? Starting from an epidemiological desert the discipline has grown remarkably, especially during the last 10-15 years: research institutes have been established, research funding has improved, multiple curriculae in Epidemiology and Public Health are offered. This increase has been quite steep, and now the epidemiological infrastructure is much better. Several medium-sized and even big population cohorts are ongoing, and the number and quality of publications from German epidemiologists has reached a respectable level. My own career in epidemiology started in the field of environmental health. After German reunification I concentrated for many years on environmental problems in East Germany and observed the health benefits after improvement of the situation. Later, I concentrated on population-based cohorts in newborns (GINI/LISA) and adults (KORA, German National Cohort), and on biobanking. This Essay describes the development in Germany after worldwar 2, illustrated by examples of research results and build-up of epidemiological infractructures worth mentioning.
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http://dx.doi.org/10.1007/s10654-017-0290-7DOI Listing
August 2017

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

Comput Math Methods Med 2017 13;2017:6742763. Epub 2017 Jul 13.

Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.
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http://dx.doi.org/10.1155/2017/6742763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5530424PMC
December 2017

Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1.

Nat Commun 2017 05 23;8:15466. Epub 2017 May 23.

Department of Ophthalmology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany.

Although lysyl oxidase-like 1 (LOXL1) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis-acting effect on the expression levels of LOXL1, mediated by differential binding of the transcription factor RXRα (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1, eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression.
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http://dx.doi.org/10.1038/ncomms15466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457519PMC
May 2017

Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors.

Nat Genet 2017 May 27;49(5):789-794. Epub 2017 Mar 27.

1st Medical Department, University Clinic Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 × 10, odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 × 10, OR = 1.24), 16p13.3 (rs2562152; P = 1.93 × 10, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 × 10, OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 × 10, OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 × 10, OR = 1.19), 1q44 (rs12076373; P = 2.63 × 10, OR = 1.23), 2q33.3 (rs7572263; P = 2.18 × 10, OR = 1.20), 3p14.1 (rs11706832; P = 7.66 × 10, OR = 1.15), 10q24.33 (rs11598018; P = 3.39 × 10, OR = 1.14), 11q21 (rs7107785; P = 3.87 × 10, OR = 1.16), 14q12 (rs10131032; P = 5.07 × 10, OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 × 10, OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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http://dx.doi.org/10.1038/ng.3823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558246PMC
May 2017

Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies.

Epidemiology 2017 03;28(2):288-299

From the aInternational Agency for Research on Cancer, Lyon, France; bThe Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; cInstitute for Risk Assessment Sciences, Utrecht, The Netherlands; dInstitute for Prevention and Occupational Medicine of the German Social Accident Insurance - Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany; eOccupational Respiratory Epidemiology, School of Population Health, University of Western Australia, Perth, Australia; fCancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piemonte, Turin, Italy; gINSERM, Centre for research in Epidemiology and Population Health (CESP), U1018, Environmental epidemiology of cancer Team, Villejuif, France; hUniversité Paris-Sud, UMRS 1018, Villejuif, France; iEpidemiology Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy; jNational Cancer Institute, Bethesda, MD; kRoy Castle Lung Cancer Research Programme, The University of Liverpool Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, Liverpool, United Kingdom; lInstitut für Epidemiologie, Deutsches Forschungszentrum fur Gesundheit und Umwelt, Neuherberg, Germany; mUniversity of Montreal Hospital Research Center (CRCHUM), Montreal, Canada; nINRS-Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada; oInstitute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany; pLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany; qThe Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), University of Oviedo, Oviedo, Spain; rRussian Cancer Research Centre, Moscow, Russia; sPublic Health Ontario, Toronto, Canada; tOccupational Cancer Research Centre, Cancer Care Ontario, Toronto, Canada; uThe Nofer Institute of Occupational Medicine, Lodz, Poland; vThe M Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland; wNational Centre for Public Health, Budapest, Hungary; xRegional Authority of Public Health, Banska Bystrica, Slovakia; yInstitute of Public Health, Bucharest, Romania; zInstitute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic; aaMasaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Department of Cancer Epidemiology & Genetics, Brno, Czech Republic; bbFaculty of Medicine, Palacky University, Olomouc, Czech Republic; ccThe Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, NY; ddNational Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; and eeDepartment of Epidemiology, ASL RomaE, Rome, Italy.

Background: Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies.

Methods: We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends.

Results: The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women.

Conclusions: Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.).
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http://dx.doi.org/10.1097/EDE.0000000000000604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287435PMC
March 2017

Federated Biobanking with Corporate Service Unit: The Munich Biobank Alliance Blueprint.

Biopreserv Biobank 2017 Feb 19;15(1):75-79. Epub 2016 Dec 19.

5 Institute for Epidemiology II , Helmholtz Center Munich, Neuherberg, Germany .

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http://dx.doi.org/10.1089/bio.2016.0101DOI Listing
February 2017

Lung Cancer Among Firefighters: Smoking-Adjusted Risk Estimates in a Pooled Analysis of Case-Control Studies.

J Occup Environ Med 2016 11;58(11):1137-1143

The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (Drs Bigert, Gustavsson); International Agency for Research on Cancer, Lyon, France (Drs Straif, Schüz, Olsson); Institute for Prevention and Occupational Medicine of the German Social Accident Insurance - Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany (Drs Taeger, Pesch, Kendzia, Brüning); Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Environmental Epidemiology of Cancer Team (Drs Stücker, Guida); Université Paris-Sud, UMRS 1018, F-94807, Villejuif, France (Drs Stücker, Guida); Institut für Epidemiologie I, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg (Dr Brüske); Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University (Dr Wichmann); Helmholtz Center Munich, Institute of Epidemiology I (Dr Wichmann); Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany (Dr Wichmann); Department of Clinical Sciences and Community Health, Università degli Studi di Milano and IRCCS Ca' Granda Foundation, Milan, Italy (Dr Pesatori); National Cancer Institute, Bethesda, Maryland (Drs Landi, Caporaso); Division of Occupational and Environmental Health, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (Drs Tse, Yu); Research Centre of University of Montréal Hospital Centre, University of Montréal, Montréal, Quebec, Canada (Drs Siemiatycki, Lavoué); Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin, Turin, Italy (Drs Richiardi, Mirabelli); Department of Environmental Medicine and Public Health, University of Padua, Padua, Italy (Dr Simonato); Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany (Dr Jöckel); Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany (Drs Ahrens, Pohlabeln); CIBERESP, University of Oviedo, Oviedo, Spain (Dr Tardón); Russian Cancer Research Centre, Moscow, Russia (Dr Zaridze); Roy Castle Lung Cancer Research Programme, Cancer Research Centre, University of Liverpool, Liverpool, UK (Dr Field); Centre for Public Health Research, Massey University, Wellington, New Zealand (Drs 't Mannetje, Pearce); Public Health Ontario, Toronto (Dr McLaughlin); Occupational Cancer Research Centre, Cancer Care Ontario, Ontario, Toronto, Canada (Dr Demers); The Nofer Institute of Occupational Medicine, Lodz (Dr Szeszenia-Dabrowska); The M Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland (Dr Lissowska); National Public Health Center, Budapest, Hungary (Dr Rudnai); Regional Authority of Public Health, Banska Bystrica, Slovakia (Dr Fabianova); Institute of Public Health, Bucharest, Romania (Dr Stanescu Dumitru); Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague (Dr Bencko); Masaryk Memorial Cancer Institute, Brno, Czech Republic (Dr Foretova); Palacky University, Faculty of Medicine, Olomouc (Dr Janout); Faculty of Medicine, Ostrava University, Ostrava, Czech Republic (Dr Janout); The Tisch Cancer Institute and Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, New York, New York (Dr Boffetta); Institute for Risk Assessment Sciences, Utrecht, the Netherlands (Drs Peters, Vermeulen, Kromhout); and Occupational Respiratory Epidemiology, School of Population Health, University of Western Australia, Perth, Western Australia, Australia (Dr Peters).

Objectives: The aim of this study was to explore lung cancer risk among firefighters, with adjustment for smoking.

Methods: We used pooled information from the SYNERGY project including 14 case-control studies conducted in Europe, Canada, New Zealand, and China, with lifetime work histories and smoking habits for 14,748 cases of lung cancer and 17,543 controls. We estimated odds ratios by unconditional logistic regression with adjustment for smoking and having ever been employed in a job known to present an excess risk of lung cancer.

Results: There was no increased lung cancer risk overall or by specific cell type among firefighters (n = 190), neither before nor after smoking adjustment. We observed no significant exposure-response relationship in terms of work duration.

Conclusions: We found no evidence of an excess lung cancer risk related to occupational exposure as a firefighter.
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http://dx.doi.org/10.1097/JOM.0000000000000878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254920PMC
November 2016

Occupational prestige, social mobility and the association with lung cancer in men.

BMC Cancer 2016 07 7;16:395. Epub 2016 Jul 7.

Roy Castle Lung Cancer Research Programme, The University of Liverpool Cancer Research Centre, Liverpool, UK.

Background: The nature of the association between occupational social prestige, social mobility, and risk of lung cancer remains uncertain. Using data from the international pooled SYNERGY case-control study, we studied the association between lung cancer and the level of time-weighted average occupational social prestige as well as its lifetime trajectory.

Methods: We included 11,433 male cases and 14,147 male control subjects. Each job was translated into an occupational social prestige score by applying Treiman's Standard International Occupational Prestige Scale (SIOPS). SIOPS scores were categorized as low, medium, and high prestige (reference). We calculated odds ratios (OR) with 95 % confidence intervals (CI), adjusting for study center, age, smoking, ever employment in a job with known lung carcinogen exposure, and education. Trajectories in SIOPS categories from first to last and first to longest job were defined as consistent, downward, or upward. We conducted several subgroup and sensitivity analyses to assess the robustness of our results.

Results: We observed increased lung cancer risk estimates for men with medium (OR = 1.23; 95 % CI 1.13-1.33) and low occupational prestige (OR = 1.44; 95 % CI 1.32-1.57). Although adjustment for smoking and education reduced the associations between occupational prestige and lung cancer, they did not explain the association entirely. Traditional occupational exposures reduced the associations only slightly. We observed small associations with downward prestige trajectories, with ORs of 1.13, 95 % CI 0.88-1.46 for high to low, and 1.24; 95 % CI 1.08-1.41 for medium to low trajectories.

Conclusions: Our results indicate that occupational prestige is independently associated with lung cancer among men.
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http://dx.doi.org/10.1186/s12885-016-2432-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936282PMC
July 2016

Genetic variants in RBFOX3 are associated with sleep latency.

Eur J Hum Genet 2016 10 4;24(10):1488-95. Epub 2016 May 4.

Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands.

Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03); combined meta-analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-)(321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.
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http://dx.doi.org/10.1038/ejhg.2016.31DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027680PMC
October 2016

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Nat Commun 2016 Feb 1;7:10494. Epub 2016 Feb 1.

Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachussetts 02215, USA.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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http://dx.doi.org/10.1038/ncomms10494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740377PMC
February 2016

Genome-wide association study identifies multiple susceptibility loci for glioma.

Nat Commun 2015 Oct 1;6:8559. Epub 2015 Oct 1.

Division of Genetics and Epidemiology, The Institute of Cancer Research, London SM2 5NG, UK.

Previous genome-wide association studies (GWASs) have shown that common genetic variation contributes to the heritable risk of glioma. To identify new glioma susceptibility loci, we conducted a meta-analysis of four GWAS (totalling 4,147 cases and 7,435 controls), with imputation using 1000 Genomes and UK10K Project data as reference. After genotyping an additional 1,490 cases and 1,723 controls we identify new risk loci for glioblastoma (GBM) at 12q23.33 (rs3851634, near POLR3B, P=3.02 × 10(-9)) and non-GBM at 10q25.2 (rs11196067, near VTI1A, P=4.32 × 10(-8)), 11q23.2 (rs648044, near ZBTB16, P=6.26 × 10(-11)), 12q21.2 (rs12230172, P=7.53 × 10(-11)) and 15q24.2 (rs1801591, near ETFA, P=5.71 × 10(-9)). Our findings provide further insights into the genetic basis of the different glioma subtypes.
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http://dx.doi.org/10.1038/ncomms9559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600760PMC
October 2015

Lung cancer among coal miners, ore miners and quarrymen: smoking-adjusted risk estimates from the synergy pooled analysis of case-control studies.

Scand J Work Environ Health 2015 Sep 8;41(5):467-77. Epub 2015 Jul 8.

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA). Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.

Objectives: Working in mines and quarries has been associated with an elevated lung cancer risk but with inconsistent results for coal miners. This study aimed to estimate the smoking-adjusted lung cancer risk among coal miners and compare the risk pattern with lung cancer risks among ore miners and quarrymen.

Methods: We estimated lung cancer risks of coal and ore miners and quarrymen among 14 251 lung cancer cases and 17 267 controls from the SYNERGY pooled case-control study, controlling for smoking and employment in other at-risk occupations.

Results: Ever working as miner or quarryman (690 cases, 436 controls) was associated with an elevated odds ratio (OR) of 1.55 [95% confidence interval (95% CI) 1.34-1.79] for lung cancer. Ore miners (53 cases, 24 controls) had a higher OR (2.34, 95% CI 1.36-4.03) than quarrymen (67 cases, 39 controls; OR 1.92, 95% CI 1.21-3.05) and coal miners (442 cases, 297 controls; OR 1.40, 95% CI 1.18-1.67), but CI overlapped. We did not observe trends by duration of exposure or time since last exposure.

Conclusions: This pooled analysis of population-based studies demonstrated an excess lung cancer risk among miners and quarrymen that remained increased after adjustment for detailed smoking history and working in other at-risk occupations. The increase in risk among coal miners were less pronounced than for ore miners or quarrymen.
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http://dx.doi.org/10.5271/sjweh.3513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334050PMC
September 2015

Whole-Body MR Imaging in the German National Cohort: Rationale, Design, and Technical Background.

Radiology 2015 Oct 19;277(1):206-20. Epub 2015 May 19.

From the German National Cohort (GNC) Consortium, Central Executive Office of the German National Cohort, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany (F.B.); Department of Clinical Radiology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany (F.B., T.H., M.F.R.); Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany (H.U.K., S.W., C.L.S., M.A.W.); Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany (M.F., S.C.L.); Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany (K.H.G., R.K.); Charité Campus Buch, ECRC Universitätsmedizin Berlin und HELIOS Klinik Berlin-Buch, Klinik für Kardiologie und Nephrologie, Berlin, Germany (J.S.); Berlin Ultrahigh Field Facility (BUFF), Max-Delbrueck Center for Molecular Medicine, Berlin, Germany (T.N.); Epidemiology Research Group, Max-Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany (T.P.); Institute of Neuroscience and Medicine (INM-1), Jülich Research Centre, Jülich, Germany (S.C., K.A.); C. and O. Vogt Institute for Brain Research, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany (K.A.); JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany (K.A.); Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany (K.B.); Department of Radiology and Neuroradiology, University Medicine Greifswald, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany (R.B., N.H., K.H.); Klinik für Diagnostische und Interventionelle Radiologie und Neuroradiologie, Klinikum Augsburg, Augsburg, Germany (T.K.); Helmholtz Zentrum München-German Research Center for Environmental Health, Munich, Germany (J.L., H.E.W.); Institute of Medical Infor

Purpose: To detail the rationale, design, and future perspective of implementing whole-body magnetic resonance (MR) imaging in the German National Cohort, a large multicentric population-based study.

Materials And Methods: All institutional review boards approved the study, and informed consent is obtained before study enrollment. Participants are enrolled from a random sample of the general population at five dedicated imaging sites among 18 recruitment centers. MR imaging facilities are equipped with identical 3.0-T imager technology and use uniform MR protocols. Imager-specific hardware and software settings remained constant over the study period. On-site and centralized measures of image quality enable monitoring of completeness of the acquisitions and quality of each of the MR sequences. Certified radiologists read all MR imaging studies for presence of incidental findings according to predefined algorithms.

Results: Over a 4-year period, six participants per day are examined at each center, totaling a final imaging cohort of approximately 30 000 participants. The MR imaging protocol is identical for each site and comprises a set of 12 native series to cover neurologic, cardiovascular, thoracoabdominal, and musculoskeletal imaging phenotypes totaling approximately 1 hour of imaging time. A dedicated analysis platform as part of a central imaging core incorporates a thin client-based integrative and modular data handling platform to enable multicentric off-site image reading for incidental findings. Scientific analysis will be pursued on a per-project hypothesis-driven basis.

Conclusion: Population-based whole-body MR imaging as part of the German National Cohort will serve to compile a comprehensive image repository, will provide insight into physiologic variants and subclinical disease burden, and has the potential to enable identification of novel imaging biomarkers of risk.
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http://dx.doi.org/10.1148/radiol.2015142272DOI Listing
October 2015

Lung cancer risk among cooks when accounting for tobacco smoking: a pooled analysis of case-control studies from Europe, Canada, New Zealand, and China.

J Occup Environ Med 2015 Feb;57(2):202-9

From the Institute of Environmental Medicine (Drs Bigert and Gustavsson), Karolinska Institutet, Stockholm, Sweden; International Agency for Research on Cancer (Drs Straif, Schüz, and Olsson), Lyon, France; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance-Institute of the Ruhr-Universität Bochum (IPA) (Drs Pesch and Brüning, Mr Kendzia), Germany; Inserm, Centre for Research in Epidemiology and Population Health (CESP) (Drs Stücker and Guida), U1018, Environmental Epidemiology of Cancer Team, F-94807, Villejuif, France; Université Paris-Sud (Drs Stücker and Guida), UMRS 1018, F-94807, Villejuif, France; Institut für Epidemiologie I (Drs Brüske and Wichmann), Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany; Department of Clinical Sciences and Community Health (Dr Pesatori), Università degli Studi di Milano, Milan, Italy; National Cancer Institute (Drs Landi and Caporaso), Bethesda, MD; Division of Occupational and Environmental Health (Drs Tse and Yu), School of Public Health and Primary Care, The Chinese University of Hong Kong, China; Research Centre of University of Montréal Hospital Centre (Drs Siemiatycki and Pintos), University of Montréal, Canada; Cancer Epidemiology Unit (Drs Merletti and Mirabelli), Department of Medical Sciences, University of Turin, Italy; Department of Environmental Medicine and Public Health (Dr Simonato), University of Padua, Italy; Institute for Medical Informatics (Dr Jöckel), Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany; Bremen Institute for Prevention Research and Social Medicine (Drs Ahrens and Pohlabeln), Bremen, Germany; CIBERESP (Dr Tardón), University of Oviedo, Spain; Russian Cancer Research Centre (Dr Zaridze), Moscow, Russia; Roy Castle Lung Cancer Research Programme, Cancer Research Centre (Dr Field), University of Liverpool, UK; Centre for Public Health Research (Drs Mannetje and Pearce), Massey University, Wellingt

Objectives: To investigate the risk of lung cancer among cooks, while controlling for smoking habits.

Methods: We used data from the SYNERGY project including pooled information on lifetime work histories and smoking habits from 16 case-control studies conducted in Europe, Canada, New Zealand, and China.

Results: Before adjustment for smoking, we observed an increased risk of lung cancer in male cooks, but not in female cooks. After adjusting, there was no increased risk and no significant exposure-response relationship. Nevertheless, subgroup analyses highlighted some possible excess risks of squamous cell carcinoma and small cell carcinoma in female cooks.

Conclusions: There is evidence that lung cancer risks among cooks may be confounded by smoking. After adjustment, cooks did not experience an increased risk of lung cancer overall. The subgroup analyses showing some excess risks among female cooks require cautious interpretation.
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http://dx.doi.org/10.1097/JOM.0000000000000337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508228PMC
February 2015

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Nat Genet 2015 Jan 24;47(1):78-83. Epub 2014 Nov 24.

1] Institute of Cardiovascular Research Royal Holloway University of London (ICR2UL), London, UK. [2] Ashford and St Peter's Hospitals, London, UK.

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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http://dx.doi.org/10.1038/ng.3154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824623PMC
January 2015

Public biobanks: calculation and recovery of costs.

Sci Transl Med 2014 Nov;6(261):261fs45

INSERM, National Biobank Infrastructure, Paris, France.

A calculation grid developed by an international expert group was tested across biobanks in six countries to evaluate costs for collections of various types of biospecimens. The assessment yielded a tool for setting specimen-access prices that were transparently related to biobank costs, and the tool was applied across three models of collaborative partnership.
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http://dx.doi.org/10.1126/scitranslmed.3010444DOI Listing
November 2014

Is previous respiratory disease a risk factor for lung cancer?

Am J Respir Crit Care Med 2014 Sep;190(5):549-59

1 International Agency for Research on Cancer, Lyon, France.

Rationale: Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously.

Objectives: Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma.

Methods: The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case-control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking.

Measurements And Main Results: Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20-1.48 and OR, 1.50; 95% CI, 1.21-1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33-4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis "only." Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter.

Conclusions: Findings from this large international case-control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer.
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http://dx.doi.org/10.1164/rccm.201402-0338OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214084PMC
September 2014

PLA1A2 platelet polymorphism predicts mortality in prediabetic subjects of the population based KORA S4-Cohort.

Cardiovasc Diabetol 2014 May 5;13:90. Epub 2014 May 5.

Heart and Diabetes Center NRW, Ruhr University Bochum, Georgstr, 11, D-32545 Bad Oeynhausen, Germany.

Objective: The genetic polymorphism concerning the ß3-subunit of platelet integrin receptor glycoprotein IIIa is held responsible for enhanced binding of adhesive proteins resulting in increased thrombogenic potential. Whether it is associated with mortality, HbA1c or platelet volume is tested prospectively in an epidemiological cohort.

Research Design And Methods: Population-based Cooperative Health Research in the Region of Augsburg (KORA) S4-Survey (N = 4,028) was investigated for prognostic value of PLA1A2-polymorphism regarding all-cause mortality, correlation with HbA1c, and mean platelet volume. Multivariate analysis was performed to investigate association between genotype and key variables.

Results: Prevalence of thrombogenic allele variant PLA2 was 15.0%. Multivariate analysis revealed no association between PLA1A2 polymorphism and mortality in the KORA-cohort. HbA1c was a prognostic marker of mortality in non-diabetic persons resulting in J-shaped risk curve with dip at HbA1c = 5.5% (37 mmol/mol), confirming previous findings regarding aged KORA-S4 participants (55-75 years). PLA1A2 was significantly associated with elevated HbA1c levels in diabetic patients (N = 209) and reduced mean platelet volume in general population. In non-diabetic participants (N = 3,819), carriers of PLA2 allele variant presenting with HbA1c > 5.5% (37 mmol/mol) showed higher relative risk of mortality with increasing HbA1c.

Conclusion: PLA1A2 polymorphism is associated with mortality in participants with HbA1c ranging from 5.5% (37 mmol/mol) to 6.5% (48 mmol/mol). Maintenance of euglycemic control and antiplatelet therapy are therefore regarded as effective primary prevention in this group.
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http://dx.doi.org/10.1186/1475-2840-13-90DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4022397PMC
May 2014

Lung cancer risk among bricklayers in a pooled analysis of case-control studies.

Int J Cancer 2015 Jan 3;136(2):360-71. Epub 2014 Jun 3.

Epidemiology Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.

Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. 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. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28-1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32-1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93-1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42-1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44-2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95-1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos.
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http://dx.doi.org/10.1002/ijc.28986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477910PMC
January 2015

Evaluation of the impact of low emission zone and heavy traffic ban in Munich (Germany) on the reduction of PM₁₀ in ambient air.

Int J Environ Res Public Health 2014 May 13;11(5):5094-112. Epub 2014 May 13.

Helmholtz Zentrum München, Institute of Epidemiology II, Ingolstädter Landstr. 1, Neuherberg 85764, Germany.

Concentrations of ambient fine particles (PM10: particles with an aerodynamic diameter ≤ 10 µm) are still exceeding current air quality standards in many European cities. In Munich (Germany), low emission zone and transit bans for heavy-duty vehicles were introduced in 2008 aiming at reduction of traffic emissions contribution to PM10. The effects of those measures on PM10 mass concentrations in Munich were investigated with a semiparametric regression model for modeling PM10 levels adjusted for time, background pollution, public holidays and wind direction. The reduction of PM10 concentration after the introduction of the measures was larger at a traffic monitoring site (13.0 %, 19.6 % in summer, and 6.8 % in winter) and smaller in urban background (4.5 %, 5.7 % in summer, and 3.2 % in winter). The effect was most pronounced on Fridays and on the weekends in summer.
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http://dx.doi.org/10.3390/ijerph110505094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053866PMC
May 2014

Mitochondrial DNA variants in obesity.

PLoS One 2014 2;9(5):e94882. Epub 2014 May 2.

Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany.

Heritability estimates for body mass index (BMI) variation are high. For mothers and their offspring higher BMI correlations have been described than for fathers. Variation(s) in the exclusively maternally inherited mitochondrial DNA (mtDNA) might contribute to this parental effect. Thirty-two to 40 mtDNA single nucleotide polymorphisms (SNPs) were available from genome-wide association study SNP arrays (Affymetrix 6.0). For discovery, we analyzed association in a case-control (CC) sample of 1,158 extremely obese children and adolescents and 435 lean adult controls. For independent confirmation, 7,014 population-based adults were analyzed as CC sample of n = 1,697 obese cases (BMI ≥ 30 kg/m2) and n = 2,373 normal weight and lean controls (BMI<25 kg/m2). SNPs were analyzed as single SNPs and haplogroups determined by HaploGrep. Fisher's two-sided exact test was used for association testing. Moreover, the D-loop was re-sequenced (Sanger) in 192 extremely obese children and adolescents and 192 lean adult controls. Association testing of detected variants was performed using Fisher's two-sided exact test. For discovery, nominal association with obesity was found for the frequent allele G of m.8994G/A (rs28358887, p = 0.002) located in ATP6. Haplogroup W was nominally overrepresented in the controls (p = 0.039). These findings could not be confirmed independently. For two of the 252 identified D-loop variants nominal association was detected (m.16292C/T, p = 0.007, m.16189T/C, p = 0.048). Only eight controls carried the m.16292T allele, five of whom belonged to haplogroup W that was initially enriched among these controls. m.16189T/C might create an uninterrupted poly-C tract located near a regulatory element involved in replication of mtDNA. Though follow-up of some D-loop variants still is conceivable, our hypothesis of a contribution of variation in the exclusively maternally inherited mtDNA to the observed larger correlations for BMI between mothers and their offspring could not be substantiated by the findings of the present study.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094882PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008486PMC
December 2014

Effect modification of the association of cumulative exposure and cancer risk by intensity of exposure and time since exposure cessation: a flexible method applied to cigarette smoking and lung cancer in the SYNERGY Study.

Am J Epidemiol 2014 Feb 18;179(3):290-8. Epub 2013 Dec 18.

The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20-30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.
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http://dx.doi.org/10.1093/aje/kwt273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895097PMC
February 2014

Lung cancer risk among hairdressers: a pooled analysis of case-control studies conducted between 1985 and 2010.

Am J Epidemiol 2013 Nov 25;178(9):1355-65. Epub 2013 Sep 25.

Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies.
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http://dx.doi.org/10.1093/aje/kwt119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813309PMC
November 2013
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