TY - JOUR T1 - Effect modification of the association between total cigarette smoking and ALS risk by intensity, duration and time-since-quitting: Euro-MOTOR JF - Journal of Neurology, Neurosurgery & Psychiatry JO - J Neurol Neurosurg Psychiatry SP - 33 LP - 39 DO - 10.1136/jnnp-2019-320986 VL - 91 IS - 1 AU - Susan Peters AU - Anne E Visser AU - Fabrizio D'Ovidio AU - Jelle Vlaanderen AU - Lützen Portengen AU - Ettore Beghi AU - Adriano Chio AU - Giancarlo Logroscino AU - Orla Hardiman AU - Elisabetta Pupillo AU - Jan H Veldink AU - Roel Vermeulen AU - Leonard H van den Berg A2 - , Y1 - 2020/01/01 UR - http://jnnp.bmj.com/content/91/1/33.abstract N2 - Background We investigated the association between cigarette smoking and risk of amyotrophic lateral sclerosis (ALS) in a pooled analysis of population-based case–control studies and explored the independent effects of intensity, duration and time-since-quitting.Methods ALS cases and controls, matched by age, sex and region, were recruited in the Netherlands, Italy and Ireland (*Euro-MOTOR project). Demographics and detailed lifetime smoking histories were collected through questionnaires. Effects of smoking status, intensity (cigarettes/day), duration (years), pack-years and time-since-quitting (years) on ALS risk were estimated using logistic regression models, adjusting for age, sex, alcohol, education and centre. We further investigated effect modification of the linear effects of pack-years by intensity, duration and time-since-quitting using excess OR (eOR) models.Results Analyses were performed on 1410 cases and 2616 controls. Pack-years were positively associated with ALS risk; OR=1.26 (95% CI: 1.03 to 1.54) for the highest quartile compared with never smokers. This association appeared to be predominantly driven by smoking duration (ptrend=0.001) rather than intensity (ptrend=0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (ptrend<0.0001). The eOR decreased with time-since-quitting smoking, until about 10 years prior to disease onset. High intensity smoking with shorter duration appeared more deleterious than lower intensity for a longer duration.Conclusions Our findings provide further support for the association between smoking and ALS. Pack-years alone may be insufficient to capture effects of different smoking patterns. Time-since-quitting appeared to be an important factor, suggesting that smoking may be an early disease trigger. ER -