The EPIC-Norfolk Study
Smoking and risk for amyotrophic lateral sclerosis: analysis of the EPIC cohort.
Annals of neurology 2009 ; 65: 378-85.
Gallo V, Bueno-de-Mesquita HB, Vermeulen R, Andersen PM, Kyrozis A, Linseisen J, Kaaks R, Allen NE, Roddam AW, Boshuizen HC, Peeters PH, Palli D, Mattiello A, Sieri S, Tumino R, Jiménez-Martín JM, Diaz MJ, Suárez LR, Trichopoulou A, Agudo A, Arriola L, Barricante-Gurrea A, Bingham S, Khaw KT, Manjer J, Lindkvist B, Overvad K, Bach FW, Tjønneland A, Olsen A, Bergmann MM, Boeing H, Clavel-Chapelon F, Lund E, Hallmans G, Middleton L, Vineis P, and Riboli E
DOI : 10.1002/ana.21653
PubMed ID : 19399866
PMCID :
URL : https://onlinelibrary.wiley.com/doi/full/10.1002/ana.21653
Abstract
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.
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.
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.
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.