Research provides insight into how night shift work increases the risk of cancer

SPOKANE, Washington. New clues as to why night shift workers are at increased risk of developing certain types of cancer are presented in a new study conducted at Washington State University Health Spokane.

Published online in the Journal of Pineal Research, the study involved a controlled laboratory experiment using healthy volunteers who scheduled after-hours or day-offs. Findings from the study suggest that night shifts disrupt natural rhythm of 24 hours in the activity of certain cancer-related genes, making night shifts workers more vulnerable to damage to their DNA, while at the same time impairing the body’s DNA repair mechanisms. deal with that damage.

Although more research is needed, these discoveries could one day be used to prevent and treat cancer in night shift workers.

“There is growing evidence that cancer is more common in night workers, which has led the World Health Organization’s International Agency for Research on Cancer to consider night shift work as a likely carcinogen,” said co-author Shobhan Gaddameedhi, associate professor. formerly at the WSU College of Pharmacy and Pharmaceutical Sciences and now at North Carolina State University’s Department of Biological Sciences and Center for Human Health and the Environment. “However, it was unclear why night shift work increases the risk of cancer, which our study seeks to address.”

Study of the rhythms in cancer-related genes

As part of a partnership between the WSU Sleep and Performance Research Center and the U.S. Department of Energy’s Pacific Northwest National Laboratory (PNNL), Gaddameedhi and other WSU scientists worked with bioinformatics experts at PNNL to explore the potential involvement of the biological clock, the body’s built-in mechanism that keeps us on a 24-hour night and day cycle. Although there is a central biological clock in the brain, almost every cell in the body also has its own built-in clock. This cellular clock involves genes known as clock genes that are rhythmic in their expression, meaning that their activity levels vary by day or day. The researchers suggested that the expression of genes associated with cancer may also be rhythmic, and that night shifts may interfere with the rhythmic action of these genes.

To test this, they conducted a simulated shift work experiment in which 14 participants spent seven days in the sleep lab at WSU Health Sciences Spokane. Half of them completed a three-day simulated night shift schedule, while the other half were on a three-day simulated shift schedule. Upon completion of their simulated shifts, all participants were kept in a constant routine protocol used to examine the internally generated biological rhythms of humans, regardless of any external influences. As part of the protocol, they were kept awake for 24 hours in a semi-oblique position under constant light exposure and room temperature and given identical snacks every hour. Every three hours a blood sample was drawn.

Analyzes of white blood cells taken from the blood samples showed that the rhythms of many of the cancer-related genes differed in the night-shift condition compared to the day-shift condition. Strikingly, genes associated with DNA repair that show clear rhythms in the day shift state have lost their rhythm in the night shift state.

The researchers looked at what the consequences might be of the changes in the expression of cancer-related genes. They found that white blood cells isolated from the blood of participants in the night shift showed more evidence of DNA damage than those of participants in the day shift. What’s more, after the researchers exposed isolated white blood cells to ionizing radiation at two different times of the day, cells irradiated in the evening showed increased DNA damage in the night shift condition compared to the day shift condition. This meant that white blood cells from participants in the night shift were more vulnerable to external damage through radiation, a known risk factor for DNA damage and cancer.

“Taken together, these findings suggest that night shifts give away the timing of the expression of cancer-related genes in a way that reduces the efficiency of the body’s DNA repair processes when it is most needed,” said co-author Jason. McDermott said. a computational scientist at the Division of Biological Sciences of the Pacific Northwest National Laboratory.

Potential for improved prevention, treatment

The next step of the researchers is to perform the same experiment with actual shift workers who have been consistent on day or night shift for years to determine whether night workers build up the irreparable DNA damage over time, which can ultimately increase the risk. of cancer. If what happens to actual shift workers is consistent with current findings, this work could eventually be used to develop prevention strategies and drugs that could address the failure of DNA repair processes. It can also be the basis for strategies to optimize the timing of cancer therapy, so that treatment is administered when the effectiveness is best and side effects are minimal, a procedure called chronotherapy, which should be tuned to the internal rhythms of night workers .

“Night shift workers face significant health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” said fellow senior author Hans Van Dongen, a professor at WSU Elson S. Floyd College of Medicine and director of the WSU Sleep and Performance Research Center. “It is high time that we find diagnostic and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”

In addition to Van Dongen, Gaddameedhi and McDermott, study authors included Bala Koritala, Kenneth Porter, Osama Arshad, Rajendra Gajula, Hugh Mitchell, Tarana Arman, Mugimane Manjanatha and Justin Teeguarden.

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