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

Olsson, Ann C.; Vermeulen, Roel; Schüz, Joachim; Kromhout, Hans; Pesch, Beate; Peters, Susan; Behrens, Thomas; Portengen, Lützen; Mirabelli, Dario; Gustavsson, Per; Kendzia, Benjamin; Almansa, Josue; Luzon, Veronique; Vlaanderen, Jelle; Stücker, Isabelle; Guida, Florence; Consonni, Dario; Caporaso, Neil; Landi, Maria Teresa; Field, John; Brüske, Irene; Wichmann, Heinz-Erich; Siemiatycki, Jack; Parent, Marie-Elise; Richiardi, Lorenzo; Merletti, Franco; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Plato, Nils; Tardón, Adonina; Zaridze, David; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Stanescu Dumitru, Rodica; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Bueno-de-Mesquita, Bas; Forastiere, Francesco; Brüning, Thomas; Straif, Kurt

doi: 10.1097/EDE.0000000000000604
Occupational Epidemiology

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,

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.

Submitted 20 October 2015; accepted 22 November 2016.

Joachim Schüz and Kurt Straif are part of a collaborative study with the State Russian Institute of Occupational Health (SRIOH) on asbestos and cancer risk, which includes financial support from SRIOH to IARC. Paolo Boffetta acted as expert witness for Edison SpA in asbestos-related litigation, outside the submitted work. Beate Pesch, Thomas Behrens, Benjamin Kendzia, and Thomas Brüning, as staff of the Institute for Prevention and Occupational Medicine (IPA), are employed at the “Berufsgenossenschaft Rohstoffe und chemische Industrie” (BG RCI), a public body, which is a member of the study’s main sponsor, the German Social Accident Insurance (DGUV). IPA is an independent research institute of the Ruhr-Universität Bochum. The authors are independent from the German Social Accident Insurance in study design, access to the collected data, responsibility for data analysis and interpretation, and the right to publish. The views expressed in this article are those of the authors and not necessarily those of the sponsor. The other authors report no conflicts of interest. The SYNERGY project is funded by the German Social Accident Insurance (DGUV), Grant FP 271. The original studies were funded as follows: in Canada by Canadian Institutes for Health Research and Guzzo-SRC Chair in Environment and Cancer, National Cancer Institute of Canada, Canadian Cancer Society, Occupational Cancer Research Centre, Workplace Safety and Insurance Board, Canadian Cancer Society, and Cancer Care Ontario; in France by the French Agency of Health Security (ANSES), Fondation de France, French National Research Agency (ANR), National Institute of Cancer (INCA), Fondation pour la Recherche Médicale, French Institute for Public Health Surveillance (InVS), Health Ministry (DGS), Organization for the Research on Cancer (ARC), and French Ministry of work, solidarity, and public function (DGT); in Germany by Federal Ministry of Education, Science, Research, and Technology (Grant 01 HK 173/0), Federal Ministry of Science (Grant 01 HK 546/8), and the Ministry of Labour and Social Affairs (Grant IIIb7-27/13); in Italy by Environmental Epidemiology Program of the Lombardy Region, INAIL, Italian Association for Cancer Research, Region Piedmont, Compagnia di San Paolo, and Lazio Region; in Poland by Polish State Committee for Scientific Research (Grant SPUB-M-COPERNICUS/P-05/ DZ-30/99/2000); in Czech Republic by MH CZ - DRO (MMCI, 00209805); in Spain by Instituto Universitario de Oncologia, Universidad de Oviedo, Asturias, Fondo de Investigacion Sanitaria (FIS) and Ciber de Epidemiologia y Salud Publica (CIBERESP); in Sweden by Swedish Council for Work Life Research and Swedish Environmental Protection Agency; in the Netherlands by Dutch Ministry of Health, Welfare and Sports, National Institute of Public Health and the Environment, and Europe Against Cancer Program; in the UK by Roy Castle Foundation; in the USA by Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD; the IARC multicenter study in Central and Eastern Europe was funded by the European Commission’s INCO Copernicus program (Contract IC15-CT96-0313).

The data and the computer code are not available for replication because the data are not publicly available.

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Correspondence: Ann C. Olsson, ENV/IARC, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France. E-mail:

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