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Original Contribution
February 2011

Smoking and Risk of Amyotrophic Lateral Sclerosis: A Pooled Analysis of 5 Prospective Cohorts

Author Affiliations

Author Affiliations: Departments of Nutrition (Drs Wang, O’Reilly, and Ascherio), Epidemiology (Drs O’Reilly, Weisskopf, and Ascherio), and Environmental Health (Dr Weisskopf), Harvard School of Public Health, and Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School (Dr Ascherio), Boston, Massachusetts; Department of Neurology and Psychiatry, School of Medicine, University of Bari, Bari, Italy (Dr Logroscino); Epidemiology Research Program, American Cancer Society, Atlanta, Georgia (Drs McCullough and Thun); Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland (Dr Schatzkin); and Cancer Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu (Dr Kolonel).

Arch Neurol. 2011;68(2):207-213. doi:10.1001/archneurol.2010.367

Background  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.

Objective  To prospectively examine the relation between smoking and ALS in 5 well-established large cohorts.

Design  Five prospective cohorts with study-specific follow-up ranging from 7 to 28 years.

Setting  Academic research.

Patients  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.

Results  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).

Conclusions  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.