TY - JOUR
T1 - Blood metal levels and amyotrophic lateral sclerosis risk
T2 - a prospective cohort
AU - Peters, Susan
AU - Broberg, Karin
AU - Gallo, Valentina
AU - Levi, Michael
AU - Kippler, Maria
AU - Vineis, Paolo
AU - Veldink, Jan
AU - van den Berg, Leonard
AU - Middleton, Lefkos
AU - Travis, Ruth C
AU - Bergmann, Manuela M
AU - Palli, Domenico
AU - Grioni, Sara
AU - Tumino, Rosario
AU - Elbaz, Alexis
AU - Vlaar, Tim
AU - Mancini, Francesca
AU - Kühn, Tilman
AU - Katzke, Verena
AU - Agudo, Antonio
AU - Goñi, Fernando
AU - Gómez, Jesús-Humberto
AU - Rodríguez-Barranco, Miguel
AU - Merino, Susana
AU - Barricarte, Aurelio
AU - Trichopoulou, Antonia
AU - Jenab, Mazda
AU - Weiderpass, Elisabete
AU - Vermeulen, Roel
N1 - This article is protected by copyright. All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - OBJECTIVE: Metals have been suggested as risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality.METHODS: A nested ALS case-control study was conducted within the prospective EPIC cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium and zinc concentrations were measured by inductively coupled plasma-mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models.RESULTS: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex and study center. Median time between blood collection and ALS death was 8 years (range 1-15). Comparing the highest with the lowest tertile, cadmium (odds ratio (OR) 2.04, 95% confidence interval (CI) 1.08-3.87) and lead (OR 1.89, 95%CI 0.97-3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR 0.50, 95%CI 0.27-0.94). Associations for cadmium and lead remained when limiting analyses to non-current smokers.INTERPRETATION: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. This article is protected by copyright. All rights reserved.
AB - OBJECTIVE: Metals have been suggested as risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality.METHODS: A nested ALS case-control study was conducted within the prospective EPIC cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium and zinc concentrations were measured by inductively coupled plasma-mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models.RESULTS: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex and study center. Median time between blood collection and ALS death was 8 years (range 1-15). Comparing the highest with the lowest tertile, cadmium (odds ratio (OR) 2.04, 95% confidence interval (CI) 1.08-3.87) and lead (OR 1.89, 95%CI 0.97-3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR 0.50, 95%CI 0.27-0.94). Associations for cadmium and lead remained when limiting analyses to non-current smokers.INTERPRETATION: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. This article is protected by copyright. All rights reserved.
U2 - 10.1002/ana.25932
DO - 10.1002/ana.25932
M3 - Article
C2 - 33068316
SN - 0364-5134
VL - 89
SP - 125
EP - 133
JO - Annals of Neurology
JF - Annals of Neurology
IS - 1
ER -