title: Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort.
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 enrollment 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Epidemiology, Public Health and Primary Care, Imperial College London, United Kingdom. v.gallo@imperial.ac.uk
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mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality*; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires