Cigarette smoking has been proposed as a risk factor for amyotrophic lateral sclerosis (ALS), but epidemiological studies supporting this hypothesis have been small and mostly retrospective.
To prospectively examine the relation between smoking and ALS in 5 well-established large cohorts.
Five prospective cohorts with study-specific follow-up ranging from 7 to 28 years.
Participants in the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, and the National Institutes of Health–AARP (formerly known as the American Association of Retired Persons) Diet and Health Study.
Main Outcome Measures
Amyotrophic lateral sclerosis deaths identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal incident ALS was also included.
A total of 832 participants with ALS were documented among 562 804 men and 556 276 women. Smokers had a higher risk of ALS than never smokers, with age- and sex-adjusted relative risks of 1.44 (95% confidence interval, 1.23-1.68; P < .001) for former smokers and 1.42 (95% confidence interval, 1.07-1.88; P = .02) for current smokers. Although the risk of ALS was positively associated with pack-years smoked (P < .001), duration of smoking (9% increase for each 10 years of smoking, P = .006), and the number of cigarettes smoked per day (10% increase for each increment of 10 cigarettes smoked per day, P < .001), these associations did not persist when never smokers were excluded. However, among ever smokers, the risk of ALS increased as age at smoking initiation decreased (P = .03).
Results of this large longitudinal study support the hypothesis that cigarette smoking increases the risk of ALS. The potential importance of age at smoking initiation and the lack of a dose response deserve further investigation.