Shift Work Linked to MS Risk in Young

Pauline Anderson

October 19, 2011

October 19, 2011 — Research out of Sweden seems to reinforce the relationship between shift work and multiple sclerosis (MS). Two new studies have shown that shift work before the age of 20 years is associated with an increased risk of developing the disease.

"This is a very important and exciting finding," lead author Anna Karin Hedström, MD, from the Institute of Environmental Medicine at the Karolinska Institute, Sweden, told Medscape Medical News. "There seems to be a critical period of time regarding the impact of shift work and MS risk, but we have no idea why."

Circadian disruption and sleep loss may contribute to the association, said Dr. Hedström.

The new research was published online October 17 in the Annals of Neurology.

Results Replicated

The analysis included 2 studies. The first, the Epidemiological Investigation of Multiple Sclerosis (EIMS), was a case-control study using incident cases. It included 1343 people with MS (mean age at onset, 33.4 years), most of whom had received the diagnosis within the previous year, and 2900 control participants. It was the first study to find a link between shift work and MS.

A second, larger study of prevalent cases, the Genes and Environment in Multiple Sclerosis (GEMS), was carried out to see whether the EIMS findings could be replicated. "This has never been done before, and we wanted to be sure that what we saw was right," explained Dr. Hedström. This second study comprised 5129 cases with MS (mean age at onset, 33 years; mean age in study, 50 years), and 4509 matched control participants, none of whom were in the EIMS study.

For this report, shift work was defined as working hours between 9 pm and 7 am.

From detailed questionnaires, researchers categorized participants into those who did and did not work shifts before the index year. Those who had worked shifts were categorized into those who were exposed at a young age (younger than 20 years) and those who had been exposed later in life. The researchers also grouped participants on the basis of the duration in years and the intensity (number of nights per month) of their shift work.

The analysis found that among those who started working shifts before age 20 years, there was a higher occurrence of MS compared with non–shift workers. The odds ratio was 1.6 in the EIMS study (95% confidence interval [CI], 1.2 - 2.1; P = .0003) and 1.3 in the GEMS study (95% confidence interval, 1.0 - 1.6; P = .046).

Shift Work Duration

The duration of shift work was also important. Among those working shifts for 3 years or longer before age 20 years, the odds ratio of developing MS was 2.0 (95% CI, 1.2 - 3.6; P = .0007) in the EIMS study and 2.1 (1.3 - 3.4; P = .008) in the GEMS study compared with those who had never worked shifts.

The researchers adjusted for smoking, education, socioeconomic circumstances, and several other factors and got similar results. "It would be terrible to publish something and get a lot of attention, and then it turned out that it wasn't right, so we've done a lot of analysis and adjusted for everything we could think of," said Dr. Hedström.

The finding of a critical early period of exposure to shift work was surprising, she added. "I didn't expect it, but there was a biological hypothesis behind it."

Research shows that early exposure to lifestyle or environmental factors such as Epstein-Barr virus infection seems to increase the risk for MS later on. Dr. Hedström mentioned a recent study that showed that obesity during adolescence increases the risk of developing MS.

"People who are obese as teenagers have about double the risk of MS later on," she said. "There's a pattern here: it's the same critical period" of being exposed to an environmental factor.

Circadian Disruption

The "biological clock" may play a role in the association between shift work and MS, said Dr. Hedström. The circadian clock influences hormones, behavior, cognitive function, metabolism cell proliferation, apoptosis, and responses to genotoxic stress. Circadian disruption results when endogenous rhythms are out of phase with the external environment. Shift work induces circadian disruption, which can desynchronize different organs, she speculated.

Sleep disruption may be another factor, said Dr. Hedström. Poor sleep or sleep deprivation affects the number of circulating lymphocytes, natural killer cells, and antibody titers. Sleep deprivation has been shown to severely disturb the functional rhythm of regulatory T cells and CD4 T cells, and it also has been associated with the elevation of proinflammatory cytokines.

Long-term sleep restriction may lead to persistent changes in the immune system and may play a role in autoimmune disease. Dr. Hedström pointed out that thyroid diseases also have been linked to sleep disruption.

Insufficient exposure to sunlight and vitamin D deficiency might also help explain the association between early exposure to shift work and increased MS, the authors write.

Dr. Hedström's advice to teenagers? "That's a difficult question, but I think that maybe if a relative has MS, then perhaps you can try to avoid shift work."

Genetic Involvement

The next step for the researchers is to analyze the blood samples donated by the study participants to see whether there is an interaction between genetics and the environment, said Dr. Hedström.

Approached for a comment, Lilly Jung Henson, MD, a neurologist at the Swedish Neuroscience Institute, Seattle, Washington, said the concept that early-age shift work can affect MS risk is "fascinating."

However, she said in an email to Medscape Medical News, "it's too early to tell what the significance of this really is."

Dr. Jung Henson questioned whether shift work necessarily translates into an effect on circadian rhythm. "Or, does it reflect something else, perhaps socioeconomic environment which requires one to do shift work?"

Coauthor Jan Hillert, MD, PhD, reports board membership with Biogen Idec; grants/grants pending from Biogen Idec, Sanofi-Aventis, Merck, and Bayer; and speaking fees from Novartis, Biogen Idec, TEVA, and Merck. Coauthor Tomas Olsson, MD, PhD, reports consultancy with Sanofi-Aventis, Biogen Idec, and Novartis and grants/grants pending with Sanofi-Aventis, Biogen Idec, and Novartis.

Ann Neurol. 2011; Published online October 17, 2011. Abstract


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