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      Smoking and Multiple Sclerosis: An Updated Meta-Analysis

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          Abstract

          Background

          Multiple sclerosis (MS) is a leading cause of disability in young adults. Susceptibility to MS is determined by environmental exposure on the background of genetic risk factors. A previous meta-analysis suggested that smoking was an important risk factor for MS but many other studies have been published since then.

          Methods/Principal Findings

          We performed a Medline search to identify articles published that investigated MS risk following cigarette smoking. A total of 14 articles were included in this study. This represented data on 3,052 cases and 457,619 controls. We analysed these studies in both a conservative (limiting our analysis to only those where smoking behaviour was described prior to disease onset) and non-conservative manner. Our results show that smoking is associated with MS susceptibility (conservative: risk ratio (RR) 1.48, 95% confidence interval (CI) 1.35–1.63, p<10 −15; non-conservative: RR 1.52, 95% CI 1.39–1.66, p<10 −19). We also analysed 4 studies reporting risk of secondary progression in MS and found that this fell just short of statistical significance with considerable heterogeneity (RR 1.88, 95% CI 0.98–3.61, p = 0.06).

          Discussion

          Our results demonstrate that cigarette smoking is important in determining MS susceptibility but the effect on the progression of disease is less certain. Further work is needed to understand the mechanism behind this association and how smoking integrates with other established risk factors.

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          Most cited references46

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          Multiple Sclerosis

          New England Journal of Medicine, 343(13), 938-952
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            Sex ratio of multiple sclerosis in Canada: a longitudinal study.

            Incidence of multiple sclerosis is thought to be increasing, but this notion has been difficult to substantiate. In a longitudinal population-based dataset of patients with multiple sclerosis obtained over more than three decades, we did not show a difference in time to diagnosis by sex. We reasoned that if a sex-specific change in incidence was occurring, the female to male sex ratio would serve as a surrogate of incidence change. Since environmental risk factors seem to act early in life, we calculated sex ratios by birth year in 27 074 Canadian patients with multiple sclerosis identified as part of a longitudinal population-based dataset. The female to male sex ratio by year of birth has been increasing for at least 50 years and now exceeds 3.2:1 in Canada. Year of birth was a significant predictor for sex ratio (p<0.0001, chi(2)=124.4; rank correlation r=0.84). The substantial increase in the female to male sex ratio in Canada seems to result from a disproportional increase in incidence of multiple sclerosis in women. This rapid change must have environmental origins even if it is associated with a gene-environment interaction, and implies that a large proportion of multiple sclerosis cases may be preventable in situ. Although the reasons why incidence of the disease is increasing are unknown, there are major implications for health-care provision because lifetime costs of multiple sclerosis exceed pound1 million per case in the UK.
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              Statistics notes. The odds ratio.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                13 January 2011
                : 6
                : 1
                : e16149
                Affiliations
                [1 ]Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
                [2 ]Department of Clinical Neurology, University of Oxford, Oxford, United Kingdom
                [3 ]Department of Physical and Theoretical Chemistry, University of Oxford, Oxford, United Kingdom
                [4 ]Barts and The London School of Medicine and Dentistry, Blizard Institute of Cell and Molecular Science, Queen Mary University of London, London, United Kingdom
                National Institutes of Health, United States of America
                Author notes

                Conceived and designed the experiments: AEH SVR GG. Analyzed the data: AEH SVR AJW GD. Contributed reagents/materials/analysis tools: AEH SVR AJW. Wrote the paper: AEH AJW GD RD GG SVR.

                Article
                PONE-D-10-00853
                10.1371/journal.pone.0016149
                3020969
                21249154
                2b7db0c6-bb28-4f32-bfa4-d100a637f3fd
                Handel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 19 August 2010
                : 14 December 2010
                Page count
                Pages: 6
                Categories
                Research Article
                Medicine
                Clinical Research Design
                Meta-Analyses
                Systematic Reviews
                Epidemiology
                Environmental Epidemiology
                Neurology
                Demyelinating Disorders
                Multiple Sclerosis
                Public Health
                Environmental Health
                Pulmonology
                Smoking Related Disorders

                Uncategorized
                Uncategorized

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