Susan Peters1,2, Karin Broberg3, Valentina Gallo4, Michael Levi3, Maria Kippler3, Paolo Vineis5, Jan Veldink2, Leonard van den Berg2, Lefkos Middleton5, Ruth C Travis6, Manuela M Bergmann7, Domenico Palli8, Sara Grioni9, Rosario Tumino10, Alexis Elbaz11,12, Tim Vlaar11,12, Francesca Mancini13,14, Tilman Kühn15, Verena Katzke15, Antonio Agudo16, Fernando Goñi17,18, Jesús-Humberto Gómez17,19, Miguel Rodríguez-Barranco17,20,21, Susana Merino22, Aurelio Barricarte17,23,24, Antonia Trichopoulou25, Mazda Jenab26, Elisabete Weiderpass26, Roel Vermeulen1,5,27. 1. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands. 2. Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands. 3. Institute of Environmental Medicine, Karolinska Institute, Solna, Sweden. 4. Centre for Primary Care and Public Health, Queen Mary University of London, London, UK. 5. School of Public Health, Imperial College London, London, UK. 6. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. 7. German Institute of Human Nutrition, Nuthetal, Germany. 8. Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network, Florence, Italy. 9. Epidemiology and Prevention Unit, IRCCS National Cancer Institute Foundation, Milan, Italy. 10. Cancer Registry and Histopathology Department, Provincial Health Company, Ragusa, Italy. 11. Public Health France, Saint-Maurice, France. 12. Paris-Sud University, UVSQ, CESP, INSERM, Paris-Saclay University, Villejuif, France. 13. Faculty of Medicine, CESP, Paris-Sud University, UVSQ, INSERM, Paris-Saclay University, Villejuif, France. 14. Gustave Roussy Institute, Villejuif, France. 15. German Cancer Research Center, Heidelberg, Germany. 16. Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Group of Research on Nutrition and Cancer, Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Spain. 17. Networked Biomedical Research Center of Epidemiology and Public Health, Madrid, Spain. 18. Biodonostia Health Research Institute; Public Health Laboratory in Gipuzkoa, Basque Government, San Sebastian, Spain. 19. Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. 20. Andalusian School of Public Health, Granada, Spain. 21. Grenada Institute of Biosanitary Research, Granada, Spain. 22. Public Health Directorate, Asturias, Spain. 23. Navarra Public Health Institute, Pamplona, Spain. 24. Navarra Institute for Health Research, Pamplona, Spain. 25. Hellenic Health Foundation, Athens, Greece. 26. International Agency for Research on Cancer, Lyon, France. 27. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Abstract
OBJECTIVE: Metals have been suggested as a 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 (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a 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 noncurrent 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. ANN NEUROL 20209999:n/a-n/a.
OBJECTIVE: Metals have been suggested as a 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 (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a 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 noncurrent 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. ANN NEUROL 20209999:n/a-n/a.
Authors: Freya Kamel; David M Umbach; Theodore L Munsat; Jeremy M Shefner; Howard Hu; Dale P Sandler Journal: Epidemiology Date: 2002-05 Impact factor: 4.822
Authors: K Teschke; A F Olshan; J L Daniels; A J De Roos; C G Parks; M Schulz; T L Vaughan Journal: Occup Environ Med Date: 2002-09 Impact factor: 4.402
Authors: Roel Vermeulen; Leonard H van den Berg; Susan Peters; Anne E Visser; Fabrizio D'Ovidio; Jelle Vlaanderen; Lützen Portengen; Ettore Beghi; Adriano Chio; Giancarlo Logroscino; Orla Hardiman; Elisabetta Pupillo; Jan H Veldink Journal: J Neurol Neurosurg Psychiatry Date: 2019-08-21 Impact factor: 10.154
Authors: Maria Wennberg; Thomas Lundh; Ingvar A Bergdahl; Göran Hallmans; Jan-Håkan Jansson; Birgitta Stegmayr; Hipolito M Custodio; Staffan Skerfving Journal: Environ Res Date: 2005-10-10 Impact factor: 6.498
Authors: E Riboli; K J Hunt; N Slimani; P Ferrari; T Norat; M Fahey; U R Charrondière; B Hémon; C Casagrande; J Vignat; K Overvad; A Tjønneland; F Clavel-Chapelon; A Thiébaut; J Wahrendorf; H Boeing; D Trichopoulos; A Trichopoulou; P Vineis; D Palli; H B Bueno-De-Mesquita; P H M Peeters; E Lund; D Engeset; C A González; A Barricarte; G Berglund; G Hallmans; N E Day; T J Key; R Kaaks; R Saracci Journal: Public Health Nutr Date: 2002-12 Impact factor: 4.022
Authors: Elisa Majounie; Alan E Renton; Kin Mok; Elise G P Dopper; Adrian Waite; Sara Rollinson; Adriano Chiò; Gabriella Restagno; Nayia Nicolaou; Javier Simon-Sanchez; John C van Swieten; Yevgeniya Abramzon; Janel O Johnson; Michael Sendtner; Roger Pamphlett; Richard W Orrell; Simon Mead; Katie C Sidle; Henry Houlden; Jonathan D Rohrer; Karen E Morrison; Hardev Pall; Kevin Talbot; Olaf Ansorge; Dena G Hernandez; Sampath Arepalli; Mario Sabatelli; Gabriele Mora; Massimo Corbo; Fabio Giannini; Andrea Calvo; Elisabet Englund; Giuseppe Borghero; Gian Luca Floris; Anne M Remes; Hannu Laaksovirta; Leo McCluskey; John Q Trojanowski; Vivianna M Van Deerlin; Gerard D Schellenberg; Michael A Nalls; Vivian E Drory; Chin-Song Lu; Tu-Hsueh Yeh; Hiroyuki Ishiura; Yuji Takahashi; Shoji Tsuji; Isabelle Le Ber; Alexis Brice; Carsten Drepper; Nigel Williams; Janine Kirby; Pamela Shaw; John Hardy; Pentti J Tienari; Peter Heutink; Huw R Morris; Stuart Pickering-Brown; Bryan J Traynor Journal: Lancet Neurol Date: 2012-03-09 Impact factor: 44.182