Laryngeal Cancer Risks in Workers Exposed to Lung Carcinogens: Exposure-Effect Analyses Using a Quantitative Job Exposure Matrix

Abstract

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 INHANCE Consortium. We used occupational histories for 2256 laryngeal cancer cases and 7857 controls recruited from 1989-2007. We assigned quantitative exposure levels for asbestos, respirable crystalline silica, chromium-VI, and chromium-VI & 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, chromium-VI & nickel) and females (asbestos, 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 & nickel); strongest associations were for asbestos at >90%ile cumulative exposure (OR=1.3, CI=1.0-1.6), respirable crystalline silica at 30+ years duration (OR=1.4, CI=1.2-1.7) and 75%-90%ile cumulative exposure (OR=1.4, CI=1.1-1.8), chromium-VI at >75%ile cumulative exposure (OR=1.9, CI=1.2-3.0), and chromium-VI & nickel at 20-29 years duration (OR=1.5, 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.