Science Spotlight

Losing more than a good night's sleep

Your internal clock regulates daily changes in your biology (also known as your circadian rhythm), including secretion of melatonin by the pineal gland, and this clock is influenced by the light that you’re exposed to each day. Melatonin helps to coordinate circadian rhythms around the body.

More than 22 million Americans work night, evening, rotating, or on-call shifts. These night shift workers are at higher risk for diseases such as cancer. Suppression of melatonin, a hormone normally produced at night when darkness occurs, and poor sleep quality may be responsible for the increased risks of various cancers among these night workers.

"For the longest time, the mechanism thought to link nightshift work and cancer, specifically breast and prostate cancers, was dysregulation of sex hormones due to melatonin disruption," states epidemiologist Dr. Parveen Bhatti of the Public Health Sciences Division.  "However, Dr. Scott Davis’ studies of shift workers here at the Center demonstrated that, despite significant disruption of melatonin, there was little evidence of effects on sex hormones. This got us interested in looking at other potential effects of melatonin suppression, including a growing body of evidence that melatonin is involved in up regulation of DNA damage repair."

Specifically, suppression of melatonin, a cellular antioxidant, likely leads to increased reactive oxygen species (ROS). Sleep disruption is also linked to increased levels of ROS and inflammation. This build up of ROS can cause damage to DNA, and thus initiate or promote carcinogenesis.

Elevated oxidative DNA damage during day sleep may cause the increased risks of multiple cancers observed among nightshift workers, however this hypothesis had not been examined by previous population-based studies. Recently, Drs. Parveen Bhatti, Scott Davis, and colleagues evaluated levels of 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, in previously collected urine samples from dayshift and nightshift workers during their respective sleep periods. The results from this study were recently presented in Occupational and Environmental Medicine.

Using two previous cross-sectional studies, the investigators used urine samples collected during a night sleep period for 217 dayshift workers and during day and night sleep (on their first day off) periods for 223 nightshift workers to measure excreted 8-OH-dG excised by DNA repair machinery. Urine levels of 6-sulfatoxymelatonin (aMT6s), a marker of circulating melatonin levels, and sleep quality data were also available.

Nightshift workers during their day sleep periods excreted 77% of the 8-OH-dG that they themselves, excreted when they slept in the night (p=0.02).  Among these nightshift workers, the melatonin marker (aMT6s) levels were positively correlated with urinary DNA damage marker (8-OH-dG) levels. These results suggest that melatonin disruption may lead to reduced DNA repair capacity, resulting in decreased excretion of 8-OH-dG, which indicates increased cellular levels of oxidative DNA damage.

According to the lead author Dr. Bhatti, "The evidence that nightshift work causes cancer is getting stronger. However, eliminating nightshift work is an impractical solution because it is an integral and often essential part of modern society. So, we need to come up with interventions to protect nightshift workers from increased cancer risks. The biological mechanism linking nightshift work to cancer has not been clear, which has been a major barrier to coming up with interventions. Our study identified decreased repair of DNA damage, specifically the damage caused by oxidative stress, as a potential underlying mechanism for increased cancer risks among nightshift workers. In fact, we found evidence that melatonin suppression among nightshift workers was responsible for this effect, meaning that melatonin supplementation among nightshift workers could be the intervention that we’ve been looking for."

What’s in store for the future? Dr. Bhatti explains, "We measured oxidative DNA damage levels in nightshift workers during their day sleep periods. The next step is to measure oxidative DNA damage levels during night work, which is something we are currently doing. If we see similar effects during night work, it will motivate the launch of a trial to evaluate the effects of melatonin supplementation among nightshift workers."

Funding for this study was provided by the V Foundation for Cancer Research and the National Cancer Institute.

Bhatti P, Mirick DK, Randolph TW, Gong JC, Buchanan DT, Zhang J, Davis S. 2016. Oxidative DNA damage during sleep periods among nightshift workers. Occupational and Environmental Medicine. 73(8): 537-544.

Davis S, Mirick DK, Chen C, Stanczyk FZ. 2012. Night shift work and hormone levels in women. Cancer Epidemiology Biomarkers & Prevention. 21(4): 609-618.

Mirick DK, Bhatti P, Chen C, Nordt F, Stanczyk FZ, Davis S. 2013. Night shift work and levels of 6-sulfatoxymelatonin and cortisol in men. Cancer Epidemiology Biomarkers & Prevention. 22(6): 1079-87.