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Smoking as a risk factor for multiple sclerosis
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.ORCID iD: 0000-0001-9581-3845
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
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2013 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, 1022-1027 p.Article in journal (Refereed) Published
Abstract [en]

Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure.

Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples.

Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression.

Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8).

Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

Place, publisher, year, edition, pages
Sage Publications, 2013. Vol. 19, no 8, 1022-1027 p.
Keyword [en]
Multiple sclerosis, case control study, risk factors in epidemiology, smoking
National Category
Neurology
Research subject
Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-63742DOI: 10.1177/1352458512470862OAI: oai:DiVA.org:umu-63742DiVA: diva2:582939
Note

First published online December 20th, 2012.

Available from: 2013-01-11 Created: 2013-01-07 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Environmental risk factors for multiple sclerosis
Open this publication in new window or tab >>Environmental risk factors for multiple sclerosis
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Miljöfaktorers betydelse för multipel skleros
Abstract [en]

Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. It usually strikes during young adulthood, and 2.5 million individuals are estimated to have the disease worldwide. The causes of MS are not known, but several factors have been shown to be associated with the risk of the disease, including certain genes, vitamin D, smoking and Epstein- Barr virus infection. Little is known about how/if these factors interact.

Methods Study I: The risk of MS by month of birth was investigated using MS cases from the Swedish MS registry and using general population controls. Studies II–V: We identified MS cases who had donated blood prior to disease onset, and MS cases whose mothers had donated blood during pregnancy, by cross-linking a database of MS cases, and a database of mothers of MS cases, to two local biobank cohorts. One of them consisted of blood samples collected during early pregnancy, and one with samples collected during health controls. Levels of 25(OH)D (25-hydroxyvitamin D), RBP (retinol binding protein, a surrogate marker for vitamin A), CRP (C- reactive protein), cotinine (a nicotine metabolite) and anti Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibodies were measured in cases and matched controls. The risk of MS by categories of these exposures was estimated in bi- and multivariable matched logistic regression models.

Results Subjects born in spring had a higher risk of MS, but no influence of early gestational levels of the measured risk factors on the risk of MS in the offspring was observed. In prospective samples from MS cases and controls, 25(OH)D levels ≥75 nmol/l, intermediate RBP levels, and elevated CRP levels in young were associated with a decreased risk of MS. Elevated cotinine levels (suggestive of smoking) and high antibody reactivity against EBNA-1 were associated with an increased risk of MS. All factors but RBP were more clearly associated with MS in young subjects.

Conclusion All factors analyzed in prospectively collected samples were associated with the risk of MS, and taken together, the data indicate that the key etiopathological events that lead to MS occur before the age of 20–30. Study II provides support for trials exploring the primary preventive potential of oral vitamin D supplementation.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2013. 54 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1545
Keyword
Multiple sclerosis, risk factors in epidemiology, prospective, month of birth, vitamin D, vitamin A, C-reactive protein, hygiene hypothesis, smoking, cotinine, Epstein-Barr virus
National Category
Neurology
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-64212 (URN)978-91-7459-545-1 (ISBN)
Public defence
2013-03-01, Hörsal E04, By 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-02-08 Created: 2013-01-21 Last updated: 2013-02-08Bibliographically approved

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