Abstract
Studies of occupational metal exposures and amyotrophic lateral sclerosis (ALS) have focused primarily on known neurotoxicants, including lead, mercury, selenium, and cadmium. However, these exposures are often co-occurring with other lesser studied metals. We conducted a population-based case-control study with the aim of assessing associations between occupational chromium, iron, and nickel exposures and risk of ALS. We identified ALS cases in Denmark from 1982 through 2013 from the Danish National Patient Registry and matched them to 100 controls based on birth year and sex. Cumulative metal exposures were estimated using job exposure matrices applied to occupational history from the Danish Pension Fund. Although mutually adjusted odds of ALS were higher in men with chromium exposures in the third quartile (aOR = 1.24; 95% CI 0.91, 1.69) and fourth quartile (aOR = 1.19; 95% CI: 0.80, 1.76) compared to those with no exposure, differences did not reach statistical significance. We also observed higher odds of ALS in women with nickel exposures in the third quartile (aOR = 2.21; 95% CI: 1.14, 4.28), but not for the fourth quartile (aOR = 0.61; 95% CI: 0.23, 1.64). Our findings do not suggest associations between occupational exposures to these metals and ALS. However, unavoidable non-differential misclassification from the use of JEMs may have masked truly increased risk.
Highlights
Amyotrophic lateral sclerosis (ALS) is a rare degenerative motor neuron disease with notable progressive muscle weakness and decline in motor function [1]
40% of subjects were born in provincial towns, and about 24% lived in Copenhagen suburbs
All models are adjusted for age, residence at birth, and socioeconomic status. * p < 0.05. In this prospective study of occupational metal exposures and ALS risk in a Danish population, results suggest that men with the highest levels of exposure to chromium may be at modestly greater risk for ALS
Summary
Amyotrophic lateral sclerosis (ALS) is a rare degenerative motor neuron disease with notable progressive muscle weakness and decline in motor function [1]. 5 to 10% of ALS cases are attributed to familial genetic susceptibility, little is understood about the exogenous factors that influence risk of ALS [3]. It has been suggested that a large portion of these sporadic ALS cases may be associated with occupational and environmental exposures [1,4,5]. Occupational exposure to metals, including chromium, iron, and nickel, is often co-occurring in industries involving welding, machinery, pigments, and metal product manufacturing [6]. Hexavalent chromium [Cr(VI)], chromium(III), chromium compounds, and nickel compounds are well-known carcinogens [7], with demonstrated mechanistic impacts on oxidative stress [8,9]
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