BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAH) occurs widely in occupational settings. We investigated the association between occupational exposure to PAH and lung cancer risk and joint effects with smoking within the SYNERGY project. METHODS: We pooled 14 case-control studies with information on lifetime occupational and smoking histories conducted between 1985 and 2010 in Europe and Canada. Exposure to benzo[a]pyrene (BaP) was used as a proxy of PAH and estimated from a quantitative general population job-exposure matrix. Multivariable unconditional logistic regression models, adjusted for smoking and exposure to other occupational lung carcinogens, estimated ORs, and 95% confidence intervals (CI). RESULTS: We included 16,901 lung cancer cases and 20,965 frequency-matched controls. Adjusted OR for PAH exposure (ever) was 1.08 (CI, 1.02-1.15) in men and 1.20 (CI, 1.04-1.38) in women. When stratified by smoking status and histologic subtype, the OR for cumulative exposure ≥0.24 BaP μg/m3-years in men was higher in never smokers overall [1.31 (CI, 0.98-1.75)], for small cell [2.53 (CI, 1.28-4.99)] and squamous cell cancers [1.33 (CI, 0.80-2.21)]. Joint effects between PAH and smoking were observed. Restricting analysis to the most recent studies showed no increased risk. CONCLUSIONS: Elevated lung cancer risk associated with PAH exposure was observed in both sexes, particularly for small cell and squamous cell cancers, after accounting for cigarette smoking and exposure to other occupational lung carcinogens. IMPACT: The lack of association between PAH and lung cancer in more recent studies merits further research under today's exposure conditions and worker protection measures.

Boston College Massachusetts

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

Center for research in Epidemiology and Population Health Exposome and Heredity team Inserm U1018 University Paris Saclay Villejuif France

Comprehensive Pneumology Center Munich Munich Germany

Dalla Lana School of Public Health University of Toronto Toronto Canada

Department of cancer epidemiology and Prevention N N Blokhin National Research Centre of oncology Moscow Russia

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

Department of Epidemiology ASL Roma E Rome Italy

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Public Health University of Oviedo ISPA and CIBERESP Oviedo Spain

Department of Social and Preventive Medicine University of Montreal Montreal Canada

Division of Cancer Epidemiology and Genetics NCI NIH Bethesda Maryland

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

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

Faculty of Health Catholic University Ružomberok Slovakia

Faculty of Health Sciences Palacky University Olomouc Czechia

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

Former senior scientist Centre for Nutrition Prevention and Health Services National Institute for Public Health and the Environment Bilthoven the Netherlands

Institut für Medizinische Informatik Biometrie Epidemiologie Ludwig Maximilians University Munich Germany

Institute and Clinic for Occupational Social and Environmental Medicine University Hospital LMU Munich Munich Germany

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 Lyon France

ISGlobal Barcelona Spain

Leibniz Institute for Prevention Research and Epidemiology BIPS Bremen Germany

Masaryk Memorial Cancer Institute Brno Czechia

National Institute of Public Health Bucharest Romania

National Public Health Center Budapest Hungary

Occupational Cancer Research Centre Ontario Health Toronto Canada

Office of Environmental Health Hazard Assessment California Environmental Protection Agency Oakland California

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

Univ Rennes Inserm EHESP Irset UMR_S 1085 Pointe à Pitre France

Zobrazit více v PubMed

Boström CE, Gerde P, Hanberg A, Jernström B, Johansson C, Kyrklund T, et al. . Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambient air. Environ Health Perspect 2002;110:451–88. PubMed PMC

Straif K, Baan R, Grosse Y, Secretan B, El Ghissassi F, Cogliano V. Carcinogenicity of polycyclic aromatic hydrocarbons. Lancet Oncol 2005;6:931–2. PubMed

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 92. Some non-heterocyclic polycyclic aromatic hydrocarbons and some related occupational exposures. Lyon, France: IARC Press; Geneva: Distributed by World Health Organization; 2010. PubMed PMC

Olsson AC, Vermeulen R, Schuz J, Kromhout H, Pesch B, Peters S, et al. . Exposure-response analyses of asbestos and lung cancer subtypes in a pooled analysis of case-control studies. Epidemiology 2017;28:288–99. PubMed PMC

Ge C, Peters S, Olsson A, Portengen L, Schüz J, Almansa J, et al. . Respirable crystalline silica exposure, smoking, and lung cancer subtype risks. a pooled analysis of case-control studies. Am J Respir Crit Care Med 2020;202:412–21. PubMed PMC

Brenner DR, Boffetta P, Duell EJ, Bickeböller H, Rosenberger A, McCormack V, et al. . Previous lung diseases and lung cancer risk: a pooled analysis from the International Lung Cancer Consortium. Am J Epidemiol 2012;176:573–85. PubMed PMC

Brüske-Hohlfeld I, Möhner M, Pohlabeln H, Ahrens W, Bolm-Audorff U, Kreienbrock L, et al. . Occupational lung cancer risk for men in Germany: results from a pooled case-control study. Am J Epidemiol 2000;151:384–95. PubMed

Consonni D, De Matteis S, Lubin JH, Wacholder S, Tucker M, Pesatori AC, et al. . Lung cancer and occupation in a population-based case-control study. Am J Epidemiol 2010;171:323–33. PubMed PMC

Fortes C, Forastiere F, Farchi S, Mallone S, Trequattrinni T, Anatra F, et al. . The protective effect of the mediterranean diet on lung cancer. Nutr Cancer 2003;46:30–7. PubMed

Guida F, Papadopoulos A, Menvielle G, Matrat M, Févotte J, Cénée S, et al. . Risk of lung cancer and occupational history: results of a French population-based case-control study, the ICARE study. J Occup Environ Med 2011;53:1068–77. PubMed

Gustavsson P, Jakobsson R, Nyberg F, Pershagen G, Järup L, Schéele P. Occupational exposure and lung cancer risk: a population-based case-referent study in Sweden. Am J Epidemiol 2000;152:32–40. PubMed

Jöckel KH, Ahrens W, Jahn I, Pohlabeln H, Bolm-Audorff U. Occupational risk factors for lung cancer: a case-control study in West Germany. Int J Epidemiol 1998;27:549–60. PubMed

Kazma R, Babron MC, Gaborieau V, Génin E, Brennan P, Hung RJ, et al. . Lung cancer and DNA repair genes: multilevel association analysis from the International Lung Cancer Consortium. Carcinogenesis 2012;33:1059–64. PubMed PMC

López-Cima MF, González-Arriaga P, García-Castro L, Pascual T, Marrón MG, Puente XS, et al. . Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer 2007;7:162. PubMed PMC

Ramanakumar AV, Parent ME, Siemiatycki J. Risk of lung cancer from residential heating and cooking fuels in Montreal, Canada. Am J Epidemiol 2007;165:634–42. PubMed

Riboli E, Kaaks R. The EPIC Project: rationaleand study design. European prospective investigation into cancer and nutrition. Int J Epidemiol 1997;26:S6–14. PubMed

Richiardi L, Boffetta P, Simonato L, Forastiere F, Zambon P, Fortes C, et al. . Occupational risk factors for lung cancer in men and women: a population-based case-control study in Italy. Cancer Causes Control 2004;15:285–94. PubMed

Scélo G, Constantinescu V, Csiki I, Zaridze D, Szeszenia-Dabrowska N, Rudnai P, et al. . Occupational exposure to vinyl chloride, acrylonitrile and styrene and lung cancer risk (Europe). Cancer Causes Control 2004;15:445–52. PubMed

Stücker I, Hirvonen A, de Waziers I, Cabelguenne A, Mitrunen K, Cénée S, et al. . Genetic polymorphisms of glutathione S-transferases as modulators of lung cancer susceptibility. Carcinogenesis 2002;23:1475–81. PubMed

Peters S, Vermeulen R, Olsson A, Van Gelder R, Kendzia B, Vincent R, et al. . Development of an exposure measurement database on five lung carcinogens (ExpoSYN) for quantitative retrospective occupational exposure assessment. Ann Occup Hyg 2012;56:70–9. PubMed

Peters S, Vermeulen R, Portengen L, Olsson A, Kendzia B, Vincent R, et al. . SYN-JEM: a quantitative job-exposure matrix for five lung carcinogens. Ann Occup Hyg 2016;60:795–811. PubMed

Lubin JH, Colt JS, Camann D, Davis S, Cerhan JR, Severson RK, et al. . Epidemiologic evaluation of measurement data in the presence of detection limits. Environ Health Perspect 2004;112:1691–6. PubMed PMC

Ahrens W, Merletti F. A standard tool for the analysis of occupational lung cancer in epidemiologic studies. Int J Occup Environ Health 1998;4:236–40. PubMed

Mirabelli D, Chiusolo M, Calisti R, Massacesi S, Richiardi L, Nesti M, et al. . [ Database of occupations and industrial activities that involve the risk of pulmonary tumors]. Epidemiol Prev 2001;25:215–21. PubMed

Boffetta P, Jourenkova N, Gustavsson P. Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons. Cancer Causes Control 1997;8:444–72. PubMed

Bosetti C, Boffetta P. Occupational exposures to polycyclic aromatic hydrocarbons, and respiratory and urinary tract cancers: a quantitative review to 2005. Ann Oncol 2007;18:431–46. PubMed

Petit P, Maître A, Persoons R, Bicout DJ. Lung cancer risk assessment for workers exposed to polycyclic aromatic hydrocarbons in various industries. Environ Int 2019;124:109–20. PubMed

Armstrong BG, Gibbs G. Exposure-response relationship between lung cancer and polycyclic aromatic hydrocarbons (PAHs). Occup Environ Med 2009;66:740–6. PubMed

Armstrong B, Hutchinson E, Unwin J, Fletcher T. Lung cancer risk after exposure to polycyclic aromatic hydrocarbons: a review and meta-analysis. Environ Health Perspect 2004;112:970–8. PubMed PMC

Mollerup S, Berge G, Baera R, Skaug V, Hewer A, Phillips DH, et al. . Sex differences in risk of lung cancer: expression of genes in the PAH bioactivation pathway in relation to smoking and bulky DNA adducts. Int J Cancer 2006;119:741–4. PubMed

Uppstad H, Osnes GH, Cole KJ, Phillips DH, Haugen A, Mollerup S. Sex differences in susceptibility to PAHs is an intrinsic property of human lung adenocarcinoma cells. Lung Cancer 2011;71:264–70. PubMed

Guo H, Huang K, Zhang X, Zhang W, Guan L, Kuang D, et al. . Women are more susceptible than men to oxidative stress and chromosome damage caused by polycyclic aromatic hydrocarbons exposure. Environ Mol Mutagen 2014;55:472–81. PubMed

Ge C, Peters S, Olsson A, Portengen L, Schüz J, Almansa J, et al. . 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;202:402–11. PubMed PMC

Teschke K, Olshan AF, Daniels JL, De Roos AJ, Parks CG, Schulz M, et al. . Occupational exposure assessment in case-control studies: opportunities for improvement. Occup Environ Med 2002;59:575–93. PubMed PMC

Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies

Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY)