Purpose and methods: To estimate the effect of exposure to smoking on the risk for multiple sclerosis (MS), we analyzed nicotine metabolite (cotinine) levels in biobank samples from 109 MS cases and 218 matched referents.
Results: Elevated cotinine levels, even modest elevations, were associated with an increased risk for MS (all other categories versus lowest: OR = 2.9; 95% CI: 1.3-6.3). A similar but non-significant risk increase was observed also in the small subset of individuals with samples collected before the onset of MS (all other categories versus lowest: OR = 2.4; 95% CI: 0.26-21). Elevated cotinine was associated with an increased risk for MS predominantly in women (all other categories versus lowest category: OR = 3.9; 95% CI: 1.3-12), whereas the risk increase in men was smaller and non-significant.
Discussion: Smoke exposure is associated with a higher risk for MS than previously estimated. There seems to be a threshold effect present in the lower range of cotinine in its relation to MS. Modestly elevated cotinine levels suggestive of passive smoking are associated with an increased risk for MS. Smoke exposure may explain the higher incidence of MS in women. These preliminary findings need to be confirmed in an expanded material of prospectively collected samples.