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; +28 more... Peeters, Petra H; Palli, Domenico; Mattiello, Amalia; Sieri, Sabina; Tumino, Rosario; Jiménez-Martín, Juan-Manuel; Díaz, María José Tormo; Suarez, Laudina Rodriguez; Trichopoulou, Antonia; Agudo, Antonio; Arriola, Larraitz; Barricante-Gurrea, Aurelio; Bingham, Sheila; Khaw, Kay-Tee; Manjer, Jonas; Lindkvist, Björn; Overvad, Kim; Bach, Flemming W; Tjønneland, Anne; Olsen, Anja; Bergmann, Manuela M; Boeing, Heiner; Clavel-Chapelon, Francoise; Lund, Eiliv; Hallmans, Göran; Middleton, Lefkos; Vineis, Paolo; Riboli, Elio; (2009) Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort. Annals of neurology, 65 (4). pp. 378-385. ISSN 0364-5134 DOI: https://doi.org/10.1002/ana.21653
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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. 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.