O6E.6 Occupational exposures and ALS: international collaborations and new ways to identify risk factors

Background Associations between occupational exposures and amyotrophic lateral sclerosis (ALS) have been suggested, but results are inconsistent. Case-control studies are best suited for inclusion of clinically confirmed incident cases, but prone to recall bias. Cohort studies are free from recall bias and may have pre-symptomatic blood stored, to inform about exposures (e.g. lead) well before disease onset. Methods An ongoing nation-wide ALS case-control study has been conducted in the Netherlands since 2006 (currently over 3000 cases and 4500 controls) to study risk factors and possible gene-environment interactions. Part of this study has been pooled with case-control studies from Ireland and Italy (Euro-MOTOR), where the same questionnaire was administered. Results Within the Euro-MOTOR study, ∼1300 cases and ∼2600 controls had full job histories available. Occupational exposures to a range of agents were assessed using job-exposure matrices. Analyses were adjusted for age, sex, centre, education, smoking and alcohol. We found significant associations between ALS and exposure to silica (OR 1.73, 95% CI 1.28–2.33), extremely low-frequency magnetic fields (OR 1.16, 95% CI 1.01–1.33) and electric shocks (OR 1.23, 95% CI 1.05–1.43), independent of the other occupational exposures studied. Future perspectives A nested ALS case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. 219 people who died from ALS have been identified, and pre-symptomatic blood samples from 168 of these cases are available for analyses. Three controls per case were selected by incidence density sampling matched by age at recruitment, sex and study centre. Metal concentrations will be analysed in the erythrocytes. This would be the first prospective study on the association between exposure to metals and ALS. Conclusion Each study design has its strengths and weaknesses, and ALS should be investigated in a range of (occupational) studies to gain better understanding of its aetiology.