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 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.