INTRODUCTION: Various established occupational lung carcinogens are also suspected risk factors for laryngeal cancer. However, individual studies are often inadequate in size to investigate this relatively rare outcome. Other limitations include imprecise exposure assessment and inadequate adjustment for confounders. METHODS: This study applied a quantitative job exposure matrix (SYN-JEM) for four established occupational lung carcinogens to five case-control studies within the International Head and Neck Cancer Epidemiology Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989 to 2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined (to address highly correlated exposures) via SYN-JEM. We assessed effects of occupational exposure on cancer risk for males (asbestos, respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined) and females (asbestos and respirable crystalline silica), adjusting for age, study, tobacco smoking, alcohol consumption, and asbestos exposure where relevant. RESULTS: Among females, odds ratios (ORs) were increased for ever versus never exposed. Among males, P values for linear trend were <0.05 for estimated cumulative exposure (all agents) and <0.05 for exposure duration (respirable crystalline silica, chromium-VI, and chromium-VI and nickel combined); strongest associations were for asbestos at >90th percentile cumulative exposure (OR = 1.3, 95% confidence interval [CI] = 1.0, 1.6), respirable crystalline silica at 30+ years duration (OR = 1.4, 95% CI = 1.2, 1.7) and 75th-90th percentile cumulative exposure (OR = 1.4, 95% CI = 1.1, 1.8), chromium-VI at >75th percentile cumulative exposure (OR = 1.9, 95% CI = 1.2, 3.0), and chromium-VI and nickel combined at 20-29 years duration (OR = 1.5, 95% CI = 1.1, 2.2). CONCLUSIONS: These findings support hypotheses of causal links between four lung carcinogens (asbestos, respirable crystalline silica, chromium-VI, and nickel) and laryngeal cancer.

Aviano Cancer Centre Aviano Italy

Cancer Registry of Norway Institute of Population based Cancer Research Oslo Norway

Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Department of Medical Sciences University of Turin Turin Italy

Epidemiology CIPE ACCAMARGO Sao Paulo Brazil

Epidemiology Group School of Medicine Medical Sciences and Nutrition University of Aberdeen United Kingdom

Escola Nacional de Saude Publica Fundacao Oswaldo Cruz Rio de Janeiro Brazil

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

From the International Agency for Research on Cancer Lyon France

Hospital de Clinicas de Porto Alegre Porto Alegre Brazil

INSERM Sorbonne Université Institut Pierre Louis d'Epidémiologie et de Santé Publique IPLESP Paris France

Institute for Risk Assessment Sciences Utrecht University The Netherlands

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

Institute of Oncology and Radiobiology Havana Cuba

Institute of Oncology Angel H Roffo University of Buenos Aires Argentina

Leibniz Institute for Prevention Research and Epidemiology BIPS Bremen Germany

School of Medicine Dentistry and Nursing College of Medical Veterinary and Life Sciences University of Glasgow Glasgow United Kingdom

School of Medicine National and Kapodistrian University of Athens Athens Greece

Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York USA

Trinity College School of Dental Science Dublin Ireland

Unit of Nutrition and Cancer Cancer Epidemiology Research Program Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Univ Rennes Inserm EHESP Irset UMR_S 1085 Pointe à Pitre France

Universidade de Sao Paulo Sao Paulo Brazil

Universidade Federal de Pelotas Pelotas Brazil

University of Heidelberg Heidelberg Germany

University of Hong Kong Hong Kong China

University of Padua Padova Italy

University of Utah Salt Lake City USA

University Paris Sud Paris Saclay University UVSQ CESP INSERM Environmental Epidemiology of Cancer Team Villejuif France

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