Smoking and risk for amyotrophic lateral sclerosis: Analysis of the EPIC cohort†
Corresponding Author
Valentina Gallo MD, MSc
Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom
Division of Neuroscience and Mental Health, Imperial College London, London, United Kingdom
Department of Epidemiology and Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, W2 1PG, London, United KingdomSearch for more papers by this authorH. Bas Bueno-De-Mesquita MD, MPH, PhD
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Search for more papers by this authorRoel Vermeulen PhD
Julius Centre, University Medical Centre Utrecht Utrecht, The Netherlands
Institute for Risk Assessment Sciences (IRAS) University, Utrecht, The Netherlands
Search for more papers by this authorPeter M. Andersen MD, DMSc
Department of Neurology, Umeå University Hospital, Umeå, Sweden
Search for more papers by this authorAndreas Kyrozis MD, PhD
Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece
Search for more papers by this authorJakob Linseisen PhD
German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorRudolph Kaaks PhD
German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorNaomi E. Allen DPhil
Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorAndrew W. Roddam DPhil
Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorHendriek C. Boshuizen PhD
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Search for more papers by this authorPetra H. Peeters MD, PhD
Julius Centre, University Medical Centre Utrecht Utrecht, The Netherlands
Search for more papers by this authorDomenico Palli MD
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence
Search for more papers by this authorAmalia Mattiello MD
Department of Clinical and Experimental Medicine, Federico II University, Naples
Search for more papers by this authorSabina Sieri PhD
Nutritional Epidemiology Unit, National Cancer Institute, Milan
Search for more papers by this authorRosario Tumino MD
Ragusa Cancer Registry, Azienda Ospedaliera “Civile MP Arezzo,” Ragusa, Italy
Search for more papers by this authorJuan-Manuel Jiménez-Martín BSc
Andalusian School of Public Health, Granada, Spain
Search for more papers by this authorMaría José Tormo Díaz MD
Epidemiology Service Murcia Health Council, Murcia, Spain
Centro de Investigación Biomédica en Red (CIBER) Epidemiología y Salud Pública, Spain
Search for more papers by this authorLaudina Rodriguez Suarez MD, MPH
Consejería de Salud y Servicios Sanitarios, Principado de Asturias, Spain
Search for more papers by this authorAntonia Trichopoulou MD
Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece
Search for more papers by this authorAntonio Agudo MD, MSc, PhD
Unit of Nutrition, Environment Cancer, Catalan Institute of Oncology, Barcelona, Spain
Search for more papers by this authorLarraitz Arriola MD, MSc
Public Health Division of Gipuzkoa, Donostia-San Sebastian, Spain
Search for more papers by this authorAurelio Barricante-Gurrea MD
Centro de Investigación Biomédica en Red (CIBER) Epidemiología y Salud Pública, Spain
Public Health Institute of Navarra, Pamplona, Spain
Search for more papers by this authorSheila Bingham PhD
Medical Research Council Dunn Human Nutrition Unit, University of Cambridge, Cambridge, United Kingdom
Search for more papers by this authorKay-Tee Khaw MBBChir
Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom
Search for more papers by this authorJonas Manjer MD, PhD
Department of Surgery, Malmö University Hospital, Malmö, Sweden
Search for more papers by this authorBjörn Lindkvist MD, PhD
Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
Search for more papers by this authorKim Overvad PhD
Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark
Search for more papers by this authorFlemming W. Bach MD
Department of Neurology, Aarhus University Hospital, Aalborg, Denmark
Search for more papers by this authorAnne Tjønneland MD, PhD
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
Search for more papers by this authorAnja Olsen MSc, PhD
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
Search for more papers by this authorManuela M. Bergmann PhD
Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany
Search for more papers by this authorHeiner Boeing PhD
Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany
Search for more papers by this authorFrancoise Clavel-Chapelon PhD
Institut National de la Sante et de la Recherche Médicale, Institut Gustave-Roussy, Villejuif, France
Search for more papers by this authorEiliv Lund MD, PhD
Institute of Community Medicine, University of Tromsø, Tromsø, Norway
Search for more papers by this authorGöran Hallmans MD, PhD
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
Search for more papers by this authorLefkos Middleton MD, FRCP
Division of Neuroscience and Mental Health, Imperial College London, London, United Kingdom
Search for more papers by this authorPaolo Vineis MD, MPH, FFPH
Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom
Search for more papers by this authorElio Riboli MD, MSc, MPH
Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom
Search for more papers by this authorCorresponding Author
Valentina Gallo MD, MSc
Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom
Division of Neuroscience and Mental Health, Imperial College London, London, United Kingdom
Department of Epidemiology and Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, W2 1PG, London, United KingdomSearch for more papers by this authorH. Bas Bueno-De-Mesquita MD, MPH, PhD
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Search for more papers by this authorRoel Vermeulen PhD
Julius Centre, University Medical Centre Utrecht Utrecht, The Netherlands
Institute for Risk Assessment Sciences (IRAS) University, Utrecht, The Netherlands
Search for more papers by this authorPeter M. Andersen MD, DMSc
Department of Neurology, Umeå University Hospital, Umeå, Sweden
Search for more papers by this authorAndreas Kyrozis MD, PhD
Department of Neurology, Eginition Hospital, University of Athens Medical School, Athens, Greece
Search for more papers by this authorJakob Linseisen PhD
German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorRudolph Kaaks PhD
German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorNaomi E. Allen DPhil
Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorAndrew W. Roddam DPhil
Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorHendriek C. Boshuizen PhD
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Search for more papers by this authorPetra H. Peeters MD, PhD
Julius Centre, University Medical Centre Utrecht Utrecht, The Netherlands
Search for more papers by this authorDomenico Palli MD
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence
Search for more papers by this authorAmalia Mattiello MD
Department of Clinical and Experimental Medicine, Federico II University, Naples
Search for more papers by this authorSabina Sieri PhD
Nutritional Epidemiology Unit, National Cancer Institute, Milan
Search for more papers by this authorRosario Tumino MD
Ragusa Cancer Registry, Azienda Ospedaliera “Civile MP Arezzo,” Ragusa, Italy
Search for more papers by this authorJuan-Manuel Jiménez-Martín BSc
Andalusian School of Public Health, Granada, Spain
Search for more papers by this authorMaría José Tormo Díaz MD
Epidemiology Service Murcia Health Council, Murcia, Spain
Centro de Investigación Biomédica en Red (CIBER) Epidemiología y Salud Pública, Spain
Search for more papers by this authorLaudina Rodriguez Suarez MD, MPH
Consejería de Salud y Servicios Sanitarios, Principado de Asturias, Spain
Search for more papers by this authorAntonia Trichopoulou MD
Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece
Search for more papers by this authorAntonio Agudo MD, MSc, PhD
Unit of Nutrition, Environment Cancer, Catalan Institute of Oncology, Barcelona, Spain
Search for more papers by this authorLarraitz Arriola MD, MSc
Public Health Division of Gipuzkoa, Donostia-San Sebastian, Spain
Search for more papers by this authorAurelio Barricante-Gurrea MD
Centro de Investigación Biomédica en Red (CIBER) Epidemiología y Salud Pública, Spain
Public Health Institute of Navarra, Pamplona, Spain
Search for more papers by this authorSheila Bingham PhD
Medical Research Council Dunn Human Nutrition Unit, University of Cambridge, Cambridge, United Kingdom
Search for more papers by this authorKay-Tee Khaw MBBChir
Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom
Search for more papers by this authorJonas Manjer MD, PhD
Department of Surgery, Malmö University Hospital, Malmö, Sweden
Search for more papers by this authorBjörn Lindkvist MD, PhD
Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
Search for more papers by this authorKim Overvad PhD
Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark
Search for more papers by this authorFlemming W. Bach MD
Department of Neurology, Aarhus University Hospital, Aalborg, Denmark
Search for more papers by this authorAnne Tjønneland MD, PhD
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
Search for more papers by this authorAnja Olsen MSc, PhD
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
Search for more papers by this authorManuela M. Bergmann PhD
Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany
Search for more papers by this authorHeiner Boeing PhD
Department of Epidemiology, German Institute of Human Nutrition, Potsdam, Germany
Search for more papers by this authorFrancoise Clavel-Chapelon PhD
Institut National de la Sante et de la Recherche Médicale, Institut Gustave-Roussy, Villejuif, France
Search for more papers by this authorEiliv Lund MD, PhD
Institute of Community Medicine, University of Tromsø, Tromsø, Norway
Search for more papers by this authorGöran Hallmans MD, PhD
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
Search for more papers by this authorLefkos Middleton MD, FRCP
Division of Neuroscience and Mental Health, Imperial College London, London, United Kingdom
Search for more papers by this authorPaolo Vineis MD, MPH, FFPH
Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom
Search for more papers by this authorElio Riboli MD, MSc, MPH
Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom
Search for more papers by this authorPotential conflict of interest: Nothing to report.
Abstract
Objective
Cigarette smoking has been reported as “probable” risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS.
Methods
A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response.
Results
A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14–3.14), while former smokers at the time of enrolment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94–2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33–3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking.
Interpretation
These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure. Ann Neurol 2009;65:378–385.
Supporting Information
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Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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