Smoking and risk for amyotrophic lateral sclerosis: Analysis of the EPIC cohort

• Published in: Annals of neurology Vol. 65; no. 4; pp. 378 - 385
• Main Authors: Gallo, Valentina, Bueno-De-Mesquita, H. Bas, Vermeulen, Roel, Andersen, Peter M., Kyrozis, Andreas, Linseisen, Jakob, Kaaks, Rudolph, Allen, Naomi E., Roddam, Andrew W., Boshuizen, Hendriek C., Peeters, Petra H., Palli, Domenico, Mattiello, Amalia, Sieri, Sabina, Tumino, Rosario, Jiménez-Martín, Juan-Manuel, Tormo Díaz, María José, Rodriguez Suarez, Laudina, Trichopoulou, Antonia, Agudo, Antonio, Arriola, Larraitz, Barricante-Gurrea, Aurelio, Bingham, Sheila, Khaw, Kay-Tee, Manjer, Jonas, Lindkvist, Björn, Overvad, Kim, W. Bach, Flemming, Tjønneland, Anne, Olsen, Anja, Bergmann, Manuela M., Boeing, Heiner, Clavel-Chapelon, Francoise, Lund, Eiliv, Hallmans, Göran, Middleton, Lefkos, Vineis, Paolo, Riboli, Elio
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2009; Wiley-Liss
• Subjects: Adult; Age Factors; Aged; Amyotrophic Lateral Sclerosis - epidemiology; Amyotrophic Lateral Sclerosis - etiology; Amyotrophic Lateral Sclerosis - mortality; Biological and medical sciences; Clinical Medicine; Cohort Studies; Europe - epidemiology; Female; Humans; International Cooperation; Kirurgi; Klinisk medicin; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Proportional Hazards Models; Risk; Sex Factors; Smoking - adverse effects; Surgery; Surveys and Questionnaires; Europe; Nervous system diseases; Central nervous system disease; Tobacco smoking; Amyotrophic lateral sclerosis; Degenerative disease; Risk analysis; Spinal cord disease
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.21653

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.