Background. The etiology of multiple sclerosis (MS) involves interactions between genetic loci and environmental factors. The area of MS epidemiology has expanded during the last years.
Objectives. To review established lifestyle/environmental risk factors for MS and a series of other potential candidades implicated in the pathogenesis of MS, and their interaction with genetics with regard to MS risk and progression.
Methods. A large number of studies have investigated the presence of interactions between risk factors in MS development. The current literature was summarized. Assessing interaction between causal factors using departure from additivity of effects as a criterion, often referred to as additive interaction, indicates action of the two factors in the same biological pathway.
Results. Apart from established lifestyle/environmental risk factors affecting MS risk (Epstein-Barr virus infection, sun exposure, vitamin D, smoking, high body mass index at young age), there is strong evidence for influence of exposure to organic solvents, passive smoking, shift work, alcohol, and dietary factors. There is also strong evidence that smoking affects the progression of MS. A number of established lifestyle/environmental factors seem to interact with MS risk human leukocyte antigen (HLA) genes, conferring a considerably higher risk of disease among genetically susceptible individuals.
Conclusion. Lifestyle/environmental factors influencing MS risk have important implications at the population level for the risk of developing the disease. Lifestyle/environmental factors interacting with MS risk HLA genes with regard to MS may share etiologic pathways underlying the disease, arguing for a primary role of the peripheral immune system driving MS.