Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Boston College Boston Massachusetts

Cancer Epidemiology Unit Department of Medical Sciences University of Turin Turin Italy

Center for Research in Epidemiology and Population Health Team Exposome and Heredity U1018 Institut national de la santé et de la recherche médicale University of Paris Saclay Villejuif France

Comprehensive Pneumology Center Munich Member of the German Center for Lung Research Munich Germany

Consortium for Biomedical Research in Epidemiology and Public Health Madrid Spain

Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada

Department of Cancer Epidemiology and Prevention N N Blokhin National Research Center of Oncology Moscow Russia

Department of Environmental Epidemiology The Nofer Institute of Occupational Medicine Lodz Poland

Department of Epidemiology Azienda Sanitaria Locale Roma E Rome Italy

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Social and Preventive Medicine University of Montreal Montreal Quebec Canada

Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland

Epidemiology Unit Department of Cancer Epidemiology and Prevention M Sklodowska Curie National Research Institute of Oncology Warsaw Poland

Epidemiology Unit Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Faculty of Health Catholic University Ružomberok Slovakia

Faculty of Mathematics and Computer Science Institute of Statistics University of Bremen Bremen Germany

Health Research Institute of Asturias University Institute of Oncology of Asturias Cajastur Social Program University of Oviedo Oviedo Spain

Institut für Medizinische Informatik Biometrie Epidemiologie Ludwig Maximilians Universität München Munich Germany

Institute and Clinic for Occupational Social and Environmental Medicine University Hospital and

Institute for Medical Informatics Biometry and Epidemiology University Hospital Essen Essen Germany

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

Institute for Risk Assessment Sciences Utrecht University Utrecht the Netherlands

Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

Institute of Epidemiology Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany

Institute of Hygiene and Epidemiology 1st Faculty of Medicine Charles University Prague Czechia

International Agency for Research on Cancer World Health Organization Lyon France

ISGlobal Barcelona Spain; and

Leibniz Institute for Prevention Research and Epidemiology Bremen Germany

Masaryk Memorial Cancer Institute Brno Czechia

National Institute of Public Health Bucharest Romania

National Public Health Center Budapest Hungary

Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek Utrecht the Netherlands

Occupational Cancer Research Centre Ontario Health Toronto Ontario Canada

Regional Authority of Public Health Banská Bystrica Slovakia

Roy Castle Lung Cancer Research Programme Department of Molecular and Clinical Cancer Medicine University of Liverpool Liverpool United Kingdom

Stony Brook Cancer Center Stony Brook University Stony Brook New York

Université Rennes Institut national de la santé et de la recherche médicale École des hautes études en santé publique Institut de recherche en santé environnement et travail UMR_S 1085 Pointe à Pitre France

Am J Respir Crit Care Med. 2024 Jan 15;209(2):128-130. doi: 10.1164/rccm.202311-2023ED. PubMed

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