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

Abstract

BackgroundWe 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.MethodsALS 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.ResultsAnalyses 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.ConclusionsOur 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.

Role of Alcohol Drinking in Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis

“…Based on the gender differences observed in ALS patients, several groups have reported that estrogen and hormonal mechanisms may also play a potential role [119]. The effects of various environmental factors, including smoking [120], trauma [121], physical activity [122], pesticides [123] and heavy metals [124] have been investigated; smoking and pesticides are potential risk factors.…”

Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort

“…(2) exclude current smokers at baseline, because cigarette smoking is a recognized source of metals and a risk factor for ALS 12,15 ; and (3) exclude ever-smokers. For the analyses on noncurrent and never-smokers, unconditional logistic regression models were applied to preserve statistical power, adjusted for the matching variables sex, age at recruitment, and study center.…”

Multicentre, prospective registry study of amyotrophic lateral sclerosis in mainland China (CHALSR): study protocol

“… 6 And EUROMOTOR ascertains a series of potential environmental risks for ALS including alcohol consumption, smoking, electric shock and other exposures. 30–33 However, most of large registers are established in western countries and the diversity of ALS among different ethnicity calls for further cohorts. Although China has a large population, which implies a considerable number of patients with ALS, there is no large-scale registry study for ALS so far, which limits the representativeness of the previous research.…”