Study of metal exposures and amyotrophic lateral sclerosis in Denmark

Abstract

Background/Aim: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor function. Although several studies have investigated exposures to known neurotoxic metals, including lead and aluminium, to our knowledge there have been no previous studies of chromium, nickel, or iron occupational exposures and risk of ALS.Methods: We conducted a nested case-control study of occupational exposures to chromium, nickel, and iron and ALS diagnosis using population-based data from Denmark. We identified ALS cases from 1982-2013 and age- and sex-matched controls. Based on employment history and validated job exposure matrices (JEMs), we estimated cumulative exposures to these metals for 1639 ALS cases and 168,194 controls. We used sex-stratified unconditional logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI) for quartile-categorized exposures, adjusting for residential location, socioeconomic status, and age. We also conducted multivariable models mutually adjusting for each metal.Results: Cumulative occupational chromium, nickel, and iron exposures were not association with ALS in men individually or mutually adjusted. Although chromium exposures in men showed higher adjusted odds for those with the 5-year lagged 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). There were no other notable results in women.Conclusion: Though previous studies have suggested that levels of chromium, iron, and nickel can contribute to pathogenesis of neurodegenerative diseases, 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.