Cigarette smoking appears to be associated with amyotrophic lateral sclerosis (ALS), although several aspects of the relationship remain unclear, results of a prospective five-cohort study indicate.

ALS, also known as Lou Gerhig’s Disease, is a neurodegenerative disorder that affects more than 5,500 patients in the U.S. each year. There is no known cause or treatment, according to background information in the study, which was published in the Archives of Neurology Feb. 2011 issue.

Although previous studies have suggested a link between cigarette smoking and ALS risk, the researchers noted that results were conflicting, possibly due to small sample sizes and selection or survival bias.

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Éilis J. O’Reilly, ScD, of Harvard University and colleagues conducted a pooled analysis of more than one million people who participated 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 Diet and Health Study. ALS occurred in 832 participants.

The researchers found that current smokers had a 1.42 relative risk for ALS (95% CI: 1.07-1.88; P<.001) compared with never smokers. However, the risk among former smokers was higher at 1.44 (95% CI: 1.23-1.68; P<.001).

ALS risk also increased with the number of pack years smoked: ≤ 20 years, RR 1.31 (95% CI 1.07 to 1.57, P=0.004); 21 to 35 years, RR 1.71 (95% CI 1.30 to 2.25, P<0.001); > 35 years, RR 1.43 (95% CI 1.13 to 1.79, P=0.002).

Other data indicated that ALS risk increases 9% for every 10 years a person smoked (P<.006), and a 10% increase with each 10 cigarette increment smoked in a day (P<.001). Risk also increased incrementally based on the age of the person at the time they started smoking — each five year younger increment was associated with a pooled 1.11 relative risk (95% CI 1.01 to 1.22; P=0.03).

The researchers wrote that the lack of consistent risk increases with pack years smoked, suggests a more complex relationship between ALS and cigarettes. They proposed several hypotheses to help explain the association:

  • Early smoking is more important because of motor neuron development during adolescence.
  • Smoking triggers neurodegeneration, but subsequent ALS progression is independent of cigarette use.
  • Long-term smokers who don’t develop the disease may have a lower susceptibility.
  • Some components in tobacco smoke may have beneficial effects that can compensate for harmful effects of other chemicals.

“Better understanding of the relationship between smoking and ALS may further the discovery of other risk factors and help elucidate the nature of the disease,” they wrote.

Further research should focus on the importance of age at smoking initiation and the lack of a dose response between smoking and ALS risk.