Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study

Abstract

Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with still unknown etiology. We aimed at investigating the association between environmental and occupational factors with ALS risk. Methods: We performed a population-based case-control study in four Italian provinces (Catania, Modena, Novara, and Reggio Emilia) by administration of tailored questionnaires to ALS cases (n = 95) and randomly selected population referents (n = 135). We estimated ALS risk by calculating the odds ratio (OR) with its 95% confidence interval (CI) using an unconditional logistic regression model. Results: We found a positive association with disease risk for history of occupation in the agricultural sector (OR = 2.09, 95% CI 0.79–7.54), especially for longer than 10 years (OR = 2.72, 95% 1.02–7.20). Overall occupational exposure to solvents also suggested a positive association, especially for thinners (OR = 2.27, 95% CI 1.14–4.54) and paint removers (OR = 2.01, 95% CI 0.90–4.48). Both occupational and environmental exposure to electromagnetic fields show a slightly increased risk with OR = 1.69 (95% CI 0.70–4.09) and 2.41 (95% CI 1.13–5.12), respectively. Occupational but not environmental exposure to pesticides (OR = 1.22, 95% CI 0.63–2.37), particularly fungicides, and exposure to metals (OR = 4.20, 95% CI 1.88–9.38), particularly lead, mercury, and selenium, showed an imprecise but positive association. Finally, there was an indication of increased risk for living in proximity to water bodies. Conclusions: Despite the caution that needs to be used due to some study limitations, such as the low number of exposed subjects and the possibility of recall bias, these results suggest the potential role of some environmental and occupational factors in ALS etiology.

Comment on: Filippini, T.; Tesauro, M.; Fiore, M.; Malagoli, C.; Consonni, M.; Violi, F.; Iacuzio, L.; Arcolin, E.; Oliveri Conti, G.; Cristaldi, A.; Zuccarello, P.; Zucchi, E.; Mazzini, L.; Pisano, F.; Gagliardi, I.; Patti, F.; Mandrioli, J.; Ferrante, M.; Vinceti, M. Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study. Int. J. Environ. Res. Public Health 2020, 17, 2882

“…A recent paper was published by Filippini et al in the International Journal of Environmental Research and Public Health (22 April 2020) reporting the results of a population-based case-control study of environmental and occupational exposures and risk of amyotrophic lateral sclerosis (ALS) in four provinces in Italy [ 1 ]. Given my similar research in this area using population-based Danish registry data to ascertain all ALS cases diagnosed in Denmark from 1982 to 2013 and lifetime occupation history, I took special interest in this manuscript and would therefore like to make some contributions to the portion of the authors’ discussion on risk associated with occupational sectors and specific occupational exposures.…”

“…The results for the Filippini et al paper demonstrate slightly increased, but not close to statistically significant, risk of ALS in men working in the agricultural sector (adjusted odds ratio (aOR) = 2.09, 95% confidence interval (CI) 0.79–7.54) [ 1 ]. Although these results are consistent with previous studies, including those of our study which reported higher odds of ALS for men working in agriculture and farming (aOR = 1.20, 95% CI 0.99–1.44) [ 2 ], it is important to note that the small sample size of the Filippini et al study, acquired from 4 provinces in Italy, may lend itself to significantly reduced power with only nine ALS cases and eight controls reporting work in this sector [ 1 ].…”

“…The authors also found significantly increased risk of ALS in men with any occupational exposure to lead (aOR = 3.66, 95% CI 1.63–8.20) [ 1 ]. However, these exposures were not lagged to assess potential differences in windows of exposures.…”

“…Lastly, I was pleased to see that the authors’ results for associations with solvents were consistent with those from our Danish population, which found no statistically significant association with overall exposure to solvents in males [ 5 ]. Notably, the Filippini et al, manuscript did observe positive associations of ALS risk with paint thinners (aOR = 2.27, 95% CI 1.14–4.54) and removers (aOR = 2.01, 95% CI 0.90–4.48) [ 1 ]. These results are also in line with our results showing increased ALS risk in men exposed to methylene chloride (aOR = 1.23, 95% CI 1.07–1.42, P = 0.003), most commonly present in paint strippers, at least 5 years prior to ALS diagnosis [ 5 ].…”

Reply to Comment on “Environmental and Occupational Risk Factors of Amyotrophic Lateral Sclerosis: A Population-Based Case-Control Study”

“…We much appreciate the positive comments and interest concerning our study on the environmental and occupational risk factors of amyotrophic lateral sclerosis (ALS) [1]. As correctly noted by these authors, in our paper we already acknowledged some limitations they outline.…”