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.).

bbFaculty of Medicine Palacky University Olomouc Czech Republic

bThe Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

ccThe Tisch Cancer Institute and Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai New York NY

cInstitute for Risk Assessment Sciences Utrecht The Netherlands

eeDepartment of Epidemiology ASL RomaE Rome Italy

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

From the aInternational Agency for Research on Cancer Lyon France

gINSERM Centre for research in Epidemiology and Population Health 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

INRS Institut Armand Frappier Université du Québec Laval Québec Canada

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance Institute of the Ruhr Universität Bochum Bochum Germany

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

Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University Department of Cancer Epidemiology and Genetics Brno Czech Republic

mUniversity of Montreal Hospital Research Center Montreal Canada

National Institute for Public Health and the Environment Bilthoven The Netherlands

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 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

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$a Olsson, Ann C $u 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.

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$a Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies / $c AC. Olsson, R. Vermeulen, J. Schüz, H. Kromhout, B. Pesch, S. Peters, T. Behrens, L. Portengen, D. Mirabelli, P. Gustavsson, B. Kendzia, J. Almansa, V. Luzon, J. Vlaanderen, I. Stücker, F. Guida, D. Consonni, N. Caporaso, MT. Landi, J. Field, I. Brüske, HE. Wichmann, J. Siemiatycki, ME. Parent, L. Richiardi, F. Merletti, KH. Jöckel, W. Ahrens, H. Pohlabeln, N. Plato, A. Tardón, D. Zaridze, J. McLaughlin, P. Demers, N. Szeszenia-Dabrowska, J. Lissowska, P. Rudnai, E. Fabianova, R. Stanescu Dumitru, V. Bencko, L. Foretova, V. Janout, P. Boffetta, B. Bueno-de-Mesquita, F. Forastiere, T. Brüning, K. Straif,

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$a 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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