Smoking and Risk for Amyotrophic Lateral Sclerosis: Analysis of the EPIC Cohort

Research output: Contribution to journalArticle


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


  • Valentina Gallo
  • H. Bas Bueno-de-Mesquita
  • Roel Vermeulen
  • Peter M. Andersen
  • Andreas Kyrozis
  • Jakob Linseisen
  • Rudolph Kaaks
  • Naomi E. Allen
  • Andrew W. Roddam
  • Hendrick C. Boshuizen
  • Petra H. Peeters
  • Domenico Palli
  • Amalia Mattiello
  • Sabina Sieri
  • Rosario Tumino
  • Juan-Manuel Jimenez-Martin
  • Maria Jose Tormo Diaz
  • Laudina Rodriguez Suarez
  • Antonia Trichopoulou
  • Antonio Agudo
  • Larraitz Arriola
  • Aurelio Barricante-Gurrea
  • Sheila Bingham
  • Kay-Tee Khaw
  • Bjorn Lindkvist
  • Kim Overvad
  • Flemming W. Bach
  • Anne Tjonneland
  • Anja Olsen
  • Manuela M. Bergmann
  • Heiner Boeing
  • Francoise Clavel-Chapelon
  • Eiliv Lund
  • Goran Hallmans
  • Lefkos Middleton
  • Paolo Vineis
  • Elio Riboli
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Surgery
Original languageEnglish
Pages (from-to)378-385
JournalAnnals of Neurology
Issue number4
Publication statusPublished - 2009
Publication categoryResearch