An age at exposure effect in the association between sun exposure and the risk of MS in Norway and Italy. The EnvIMS study

Background: Vitamin D insufficiency is one of the factors that most consistently have been shown to be associated with an increased risk of developing multiple sclerosis (MS). This study aims to estimate the association between sun exposure as an indirectmeasure of vitamin D status at various age periods during childhood and adolescence and the risk of MS and to look for possible differences between Norway and Italy. Methods: The data for this study are from EnvIMS, a large multinational case-control study, and includes 733 cases and 1438 population based controls from Italy and 959 cases and 1718 population based controls from Norway. The exposure information was collected by means of a standardized self-administered questionnaire that included questions about sun habits during different periods in childhood and adolescence. The participants were asked to recall the amount of time spent outdoors and use of sunscreen during the same time periods. Effect estimates were calculated using logistic regression contrasting “no outdoor activity” with “being outside most of the time ” adjusting for relevant possible confounding factors. Results: Adjusting for sex we found a significant inverse association between time spent outdoors and MS both in Norway and in Italy. In Norway the association was strongest with little sun exposure in the summer between age 16 and 18 years (OR=1.79, 95% Cl[1.28 - 2.52]), while the period from age 0 to 5 years showed the strongest effect in Italy (OR= 1.57, 95% Cl [1.17 - 2.12]). We also found a statistically significant inverse association in the winter in Italy (OR= 1.45, 95% Cl [1.05 - 2.00]), but not in Norway. High sunscreen use between the age of 0 and 6 years was associated with an increased risk of MS in Norway (OR=1.59, 95% Cl [1.23 - 2.04]) after adjusting for sun exposure during the same period. Conclusion: Sun exposure was found to be inversely associated with MS both in Norway and in Italy, with the strongest effect in early childhood in Italy and in late adolescence in Norway. The effect of seasonal variations was greater in Norway with no association with sun exposure in the winter. Further, high use of sunscreen in early childhood was linked to MS in Norway. Using sun exposure as a proxy of vitamin D exposure, this study gives further support for the importance of vitamin D in relation to MS. The findings suggest a possible age variation related to country/latitude in risk of MS due to vitamin D insufficiency.