The role of past sun exposure in Multiple Sclerosis

This epidemiological thesis firstly reviews the disease Multiple Sclerosis (MS): its history, pathology, clinical expression, and the current views on immunopathogenesis, aetiology and treatment. A separate review on ultraviolet radiation (UVR) and MS indicates that recent work in photoimmunology provides evidence that UVR can attenuate T helper 1 cell mediated processes through several mechanisms, and that epidemiological features of MS, such as the striking latitudinal gradient and seasonal variation in month of birth, MS onset and disease activity, are at least in part consistent with the hypothesis that UVR exposure may reduce the risk of MS. An ecological analysis was conducted as part of the PhD to demonstrate that regional variation in MS prevalence in the continent of Australia could be closely predicted by regional UVR levels, but analytical epidemiological studies are required to further investigate the UVR hypothesis. The project central to this thesis was a population based case-control study on Multiple Sclerosis, conducted in Tasmania, Australia. It examined: (i) whether high past sun exposure was associated with a reduced risk of MS, (ii) whether sibship structure and past infections influenced the risk of MS and (iii) whether having had children and differences in prevalence and strength of MS risk factors between men and women could explain the sex difference in MS. Interviews were conducted with 136 cases with MS and 272 controls randomly drawn from the community and matched on sex and birth year. In one of the methodology chapters, a measure-retest and method comparison was conducted to examine aspects of reliability of the sun exposure measures used in the case-control study. A separate study on 104 healthy volunteers was carried out to examine the effect of seasonal variation and body hair on melanin density estimates based on skin reflectance. The case-control study showed that higher past sun exposure, particularly during childhood and early adolescence, was associated with a reduced risk of MS, which is compatible with UVR having a protective role against MS. Having younger siblings, but not older siblings, was also associated with a reduced risk of MS, while having had glandular fever or having high antibody titers against the Epstein-Barr virus was associated with an increased risk of MS. Among women, a negative association was found between having had children and MS. The finding of an inverse association between sun exposure during childhood and early adolescence and MS, if confirmed in future work, will have important public health implications.