Multicentre, population-based, case-control study of particulates, combustion products and amyotrophic lateral sclerosis risk

Objective To investigate whether exposure to particulates and combustion products may explain the association between certain occupations and amyotrophic lateral sclerosis (ALS) risk in a large, multicentre, population-based, case-control study, based on full job histories, using job-exposure matrices, with detailed information on possible confounders. Methods Population-based patients with ALS and controls were recruited from five registries in the Netherlands, Ireland and Italy. Demographics and data regarding educational level, smoking, alcohol habits and lifetime occupational history were obtained using a validated questionnaire. Using job-exposure matrices, we assessed occupational exposure to silica, asbestos, organic dust, contact with animals or fresh animal products, endotoxins, polycyclic aromatic hydrocarbons and diesel motor exhaust. Multivariate logistic regression models adjusting for confounding factors were used to determine the association between these exposures and ALS risk. Results We included 1557 patients and 2922 controls. Associations were positive for all seven occupational exposures (ORs ranging from 1.13 to 1.73 for high vs never exposed), and significant on the continuous scale for silica, organic dust and diesel motor exhaust (p values for trend ≤0.03). Additional analyses, adding an exposure (one at a time) to the model in the single exposure analysis, revealed a stable OR for silica. We found similar results when patients with a C9orf72 mutation were excluded. Conclusion In a large, multicentre study, using harmonised methodology to objectively quantify occupational exposure to particulates and combustion products, we found an association between ALS risk and exposure to silica, independent of the other occupational exposures studied.