Sleep Disorders | Sleep Review
A new study, conducted at Washington State University’s (WSU) Health Sciences Spokane, provides new clues as to why night shift workers are at increased risk of developing certain types of cancer.
The study, published online in the Journal of Pineal Research, included a controlled laboratory experiment that included healthy volunteers who had simulated night or day shift schedules. The results of the study suggest that night shifts disrupt the natural 24-hour rhythm of the activity of certain cancer-related genes, making night shift workers more susceptible to damage to their DNA, while at the same time improperly tuning the body’s DNA repair mechanisms to deal with that damage.
While more research is needed, these discoveries could one day help prevent and treat cancer in night shift workers.
“There is growing evidence that cancer is more common among night shift workers, prompting the World Health Organization’s International Agency for Research on Cancer to classify night shift work as likely carcinogenic,” says co-author Shobhan Gaddameedhi, PhD, in a press release an associate professor at WSU College in Pharmacy and Pharmaceutical Sciences and now at the Institute of Life Sciences and the Center for Human Health and Environment at North Carolina State University. “However, it was unclear why night shift work increases the risk of cancer, which our study aimed to address.”
[RELATED: More DNA Breaks Found in Doctors Who Work Overnight Shifts]
Investigation of rhythms in cancer-related genes
As part of a partnership between the WSU Research Center for Sleep and Performance and the US Department of Energy’s Pacific Northwest National Laboratory (PNNL), Gaddameedhi and other WSU scientists worked with bioinformatics experts at the PNNL to investigate the potential involvement of the biological clock, the Body to examine Built-in mechanism that keeps us on a 24-hour day and night cycle. Although there is a central biological clock in the brain, almost every cell in the body also has its own clock. These cellular clocks are genes known as clock genes that are rhythmic in expression, meaning that their levels of activity vary with the time of day or night. The researchers hypothesized that the expression of genes associated with cancer could also be rhythmic and that night shift work could disrupt the rhythmicity of these genes.
To test this, they carried out a simulated shift work experiment in which 14 participants spent 7 days in the sleep laboratory at WSU Health Sciences Spokane. Half of them completed a three-day simulated night shift schedule, while the other half completed a three-day simulated day shift schedule. After completing their simulated shifts, all participants were kept in a constant routine protocol with which the internally generated biological rhythms of humans are examined independently of external influences. As part of the protocol, they were kept awake in a semi-reclined position under constant lighting and room temperature for 24 hours and given identical snacks every hour. A blood sample was taken every three hours.
Analyzes of white blood cells from the blood samples showed that the rhythms of many cancer-related genes were different on the night shift than on the day shift. In particular, genes related to DNA repair, which showed different rhythms in the day shift, lost their rhythmicity in the night shift.
The researchers then investigated what consequences the changes in the expression of cancer-related genes could have. They found that white blood cells isolated from the blood of night shift workers showed more evidence of DNA damage than those of day shift workers. After the researchers exposed isolated white blood cells to ionizing radiation at two different times of the day, cells that were irradiated in the evening showed increased DNA damage on the night shift compared to the day shift. This meant that white blood cells from night shift workers were more susceptible to external radiation damage, a known risk factor for DNA damage and cancer.
“Taken together, these results suggest that night shift schedules postpone the timing of cancer-related genes being expressed in ways that reduce the effectiveness of the body’s DNA repair processes when they are most needed,” says co-author Jason McDermott. PhD, a computer scientist in the Biological Sciences division of the Pacific Northwest National Laboratory, in a press release.
Potential for improved prevention, treatment
The researchers’ next step is to conduct the same experiment on real shift workers, who have been working day or night shifts regularly for many years, to see if night workers have the unrepaired DNA damage built up over time, which ultimately increases the risk could increase from cancer. Ultimately, if what happens to shiftworkers in the real world is consistent with current evidence, that work could ultimately be used to develop prevention strategies and drugs that could address the malfunction of DNA repair processes. It could also form the basis of strategies to optimize the timing of cancer therapy so that treatment is delivered when it is most effective and side effects are minimal. This procedure is known as chronotherapy and would have to be adjusted to the internal rhythm of the night workers.
“Night shift workers face significant health disparities, ranging from an increased risk of metabolic and cardiovascular disease to mental disorders and cancer,” says co-senior author Hans Van Dongen, PhD, professor at Elson S. Floyd College of Medicine and WSU Director of the WSU Sleep and Performance Research Center, in a press release. “It is high time to find diagnostic and treatment solutions for this underserved group of workers so that the medical community can address their unique health challenges.”
In addition to Van Dongen, Gaddameedhi, and McDermott, the study’s authors included Bala Koritala, Kenneth Porter, Osama Arshad, Rajendra Gajula, Hugh Mitchell, Tarana Arman, Mugimane Manjanatha, and Justin Teeguarden.
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