Smoking and Increased Risk of Multiple Sclerosis: Parallel Trends in the Sex Ratio Reinforce the Evidence

PURPOSE: Smoking behavior in industrialized nations has changed markedly over the second half of the 20th century, with diverging patterns in male and female smoking rates. We examined whether the female/male incidence of multiple sclerosis (MS) changed concomitantly with smoking, as would be expected if smoking truly increased MS risk. METHODS: We identified relevant studies reporting male and female age-specific incidence of MS throughout the world using within-country birth cohorts as units of observation. We then correlated the male/female ratio of MS incidence in each birth cohort with the corresponding male/female ratios in smoking behavior obtained from national statistics. We also examined in depth the within-country trends of smoking and MS in Canada and Denmark, two populations in which statistics on MS are readily available. RESULTS: We show that, on the natural log scale, the gender ratio of MS is correlated with the gender ratio of smoking (r = 0.16; 95% confidence interval [CI]: 0.06, 0.26; p = 0.002). Additionally, we estimated an overall incidence rate ratio of 1.50 (95% CI: 1.17, 2.01) of MS for ever-smokers as compared with never-smokers. The trend in the gender ratio of smoking, however, is driven by a decline in smoking among men, rather than by an increase in women as observed for MS incidence. CONCLUSIONS: Our results are consistent with the hypothesis that smoking increases the risk of MS and explains in part the divergence in MS incidence rates in men and women. Some other factor, however, must account for the increasing MS incidence among women. Ann Epidemiol 2011;21:536-542. (C) 2011 Elsevier Inc. All rights reserved.