Effect modification of the association between total cigarette smoking and ALS risk by intensity, duration and time-since-quitting: Euro-MOTOR

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.