Smoking and the risk of amyotrophic lateral sclerosis: A systematic review and meta-analysis

Background: Epidemiologic studies have provided inconsistent results on the association of cigarette smoking with the incidence of amyotrophic lateral sclerosis (ALS). To summarise published evidence and explore sources of heterogeneity, we conducted a systematic review and meta-analysis of studies that evaluated this association. Methods: Published studies evaluating the association of smoking with incidence of ALS were searched in bibliographic databases, with relevant information collected from each article. A random effects approach was used to pool the relative rate (RR) estimates from different studies. Between study heterogeneity was explored with a meta-regression approach. Results: 18 publications reported associations between smoking and ALS risk in 15 case control studies and five cohort studies. The pooled RR (95% CI) of ALS was 1.28 (0.97 to 1.68) for current versus never smokers and 1.12 (0.98 to 1.27) for ever versus never smokers. The study specifics RRs were heterogeneous (p<0.01). The proportion of women in the study population explained 46% of between study variability. The estimated RR (95% CI) of ALS for ever versus never smokers was 0.86 (0.71 to 1.03) in men and 1.66 (1.31 to 2.10) in women. Interpretation: This meta-analysis does not support an overall strong association of smoking with ALS risk but suggests that smoking might be associated with a higher risk of ALS in women.