Childhood Sun Exposure May Lower Multiple Sclerosis Risk

LOS ANGELES, July 24 -- Exposure to the sun may be a risk factor for skin cancer, but it seems to have a protective effect against multiple sclerosis, according to a twin study.

In a study of 79 pairs of monozygotic twins, the twin who spent more hours outdoors as a child had a 25% to 57% reduced risk of developing MS, Thomas M. Mack, M.D., M.P.H., of the University of Southern California, and colleagues, reported in the July 24 issue of Neurology.

Despite a strong genetic component, with an approximately 20% concordance among identical twins, environmental effects have been suggested by the role of latitude and of migration within genetically uniform groups, the researchers said.

To eliminate genetic confounding, the researchers sought twins, at least one of whom had MS, by yearly newspaper advertisements throughout North America from 1980 through 1992. Diagnosis was verified by updated medical documentation through 2005.

The analysis was limited to monozygotic twin pairs in which only one of the pair had MS and their childhood exposure to the sun differed. The twins had ranked themselves before 1993 in relation to each of nine childhood sun-exposure activities.

The diagnoses of the twin cases occurred between the ages of 15 and 50, with roughly two-thirds diagnosed from age 20 to 40.

Sun exposure included nine activities, those in the four major seasons, on hot and cold days, and time spent sun tanning, at the beach, or playing team sports. A sun exposure index was calculated as the sum of those exposures for which one twin ranked higher than his or her co-twin.

The odds ratio (OR) for MS ranged from 0.25 to 0.57, depending on the activity and the time of year.

For example, the risk of MS was substantially lower (OR 0.40, 95% CI 0.19 to 0.83, P=0.06) for the twin who spent more time sun tanning than for his or her sibling. For twins who spent more time playing team sports, the OR was 0.44 (CI, 0.19-1.02, P=0.06).

For each unit increase in the sun index, the relative risk of MS decreased by 25%, independent of birthplace and age at diagnosis, the researchers said.

The protective influence was seen among female twins only, they noted, but added that this novel finding must be viewed with caution because only 13 male pairs were involved in the study.

Exposure to sunlight might induce protection against an autoimmune disease by any of several immunosuppressive mechanisms, the researchers said. Ultraviolet radiation may exert its effect directly by producing cytokines, and reducing natural killer cell activity, thus affecting innate immunity.

Ultraviolet radiation can also act indirectly by producing vitamin D and suppressing melatonin secretion, with the resultant effects on Th1-Th2 balance, they speculated.

This effect is probably achieved by activated vitamin D suppressing production of cytokines associated with MS activity, such as IL-2, and tumor necrosis factor alpha, and stimulating opposing cytokines, the researchers said.

Because the researchers used relative exposure within pairs and were unable to directly quantify exposure, they could not estimate the level of exposure that might confer protection, and such estimates would be inaccurate under any circumstances, they said.

Furthermore, estimates of "time spent in the sun" or "in outdoor activities" involve substantial recall bias, given the long interval between sun exposure and diagnosis, the researchers said.

This study, Dr. Mack and his colleagues wrote, reports the importance of sun exposure among individuals with identical genetic risks. "Studies of the pathway by which sun exposure reduces MS risk should receive high priority if we are to unravel the mystery of MS etiology," they concluded.