Smoking and Risk of Amyotrophic Lateral Sclerosis

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Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons affecting more than 5500 newly diagnosed patients every year in the United States.1 The consequence of ALS is a dramatic rapid deterioration of motor function.2 There is no cure for ALS, and the few available treatments have limited efficacy.1 About 90% of ALS cases are sporadic and of unknown, possibly environmental, origin.3 Cigarette smoking might contribute to the risk of ALS by a direct neurotoxic effect on motor neurons or by an increase in oxidative stress. Although the author of a 2009 review suggests that smoking can be considered an established risk factor for ALS, there have been few investigations, and results have been conflicting.4 A positive association between smoking and ALS has been reported in some case-control studies5-7 but not all of them.8-13 These discrepancies may in part be explained by small sample sizes and possible survival, selection, and recall bias.8-13 However, results of previous longitudinal studies14,15 have also been conflicting. In the Cancer Prevention Study II (CPS-II), an analysis that included 621 ALS deaths found that cigarette smoking was associated with increased ALS mortality in women but not in men.14 The lack of association between smoking and ALS in men was confirmed among a cohort of male construction workers in Sweden, 160 of whom died of ALS.15 However, in a 2009 multicenter prospective study16 in Europe that included 118 participants with ALS, current smokers had 2-fold increased rates of ALS compared with never smokers, with no significant differences by sex.

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