An international case-control study of risk factors for multiple sclerosis

Background: Recent research has raised the level of confidence in a limited number of putative environmental risk factors for multiple sclerosis (MS). While some risk factors found in early case-control studies have been confirmed in more rigorous prospective studies, these studies have not had the statistical power to examine interactions amongst these risk factors. Objective: To examine the independent and joint role of Epstein-Barr virus infection, vitamin D through diet and sunlight exposure, and smoking on the risk of MS. Methods: A case-control study that will include more than 3000 MS cases and 15,000 population controls from Norway, Italy, Sweden, Serbia and Canada is underway. A standardized questionnaire with common content for all countries that is flexible enough to accommodate the variability in risk factor distributions (for example, diet) in the different countries has been developed. Results: The questionnaire has been piloted in Norway, Serbia, Sweden and Italy on a combined total of 80 MS patients and 177 healthy subjects. Preliminary results indicate that both groups found the questions easy to understand. Findings from this pilot will be used to improve the questionnaire, reducing misclassification of exposures. Conclusions: This casecontrol study is an important step forward in MS epidemiological research and is the first of a new generation of MS etiological research focusing on selected risk factors that are individually supported in the literature and incorporating a conceptual model of their interaction. The conduct of the study in both high-risk and medium-risk countries using a common methodology is novel. The questionnaire developed in this study could be eventually adopted by researchers in other countries allowing comparison (and pooling) of data with this international initiative.