Research offers insights into how night work increases cancer risk

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

Published online at Journal of Pineal Research, the study involved a controlled laboratory experiment that used healthy volunteers who were on simulated night or day shifts. The study results suggest that night shifts disrupt natural 24-hour rhythms in the activity of certain cancer-related genes, making night workers more vulnerable to damage to their DNA and, at the same time, causing the mechanisms of repair of the body’s DNA are poorly programmed to deal with this damage.

While more research remains to be done, these findings may someday be used to help prevent and treat cancer in night workers.

“There is growing evidence that cancer is more prevalent in night workers, which has led the World Health Organization’s International Cancer Research Agency to classify night work as a probable carcinogen,” said co-author Shobhan Gaddameedhi, associate professor. formerly at the Faculty of Pharmacy and Pharmaceutical Sciences at WSU and now at the Department of Biological Sciences and Center for Human Health and Environment at North Carolina State University. “However, it is not clear why night work increases the risk of cancer, which our study sought to address.”

Studying the rhythms in cancer-related genes

As part of a partnership between the WSU Sleep and Performance Research Center and the US Department of Energy’s National Pacific Northwest Laboratory (PNNL), Gaddameedhi and other WSU scientists worked with PNNL bioinformatics experts to study the Potential involvement of the biological clock, the body’s integrated 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 built-in clock. This cell clock involves genes known as clock genes that are rhythmic in expression, meaning that their activity levels vary with the time of day or night. The researchers hypothesized that the expression of genes associated with cancer can also be rhythmic, and that night work can interrupt the rhythmicity of these genes.

To test this, they conducted a simulated work experiment in which 14 participants spent seven days inside the sleep laboratory 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 day shift schedule. After completing their simulated shifts, all participants were kept on a constant routine protocol that is used to study the biological rhythms generated internally by humans, regardless of any external influences. As part of the protocol, they were kept awake for 24 hours in a semi-reclined posture under constant exposure to light and room temperature and were given identical snacks every hour. A blood sample was collected every three hours.

Analyzes of white blood cells taken from blood samples showed that the rhythms of many of the cancer-related genes were different in the night shift compared to the day shift. Notably, genes related to DNA repair that showed different rhythms in the day shift lost their rhythm in the night shift.

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

“Together, these results suggest that the hours of the night shift alter the time of expression of cancer-related genes in a way that reduces the effectiveness of the body’s DNA repair processes when they are most needed,” said co-author Jason McDermott, a computer scientist in the Division of Biological Sciences at Pacific Northwest National Laboratory.

Potential to improve prevention, treatment

The researchers’ next step is to conduct the same experiment with real-world shift workers who have been consistently on day or night shifts for many years to determine whether unrepaired DNA damage in night workers increases over time, which can, in turn, ultimately increase the risk of cancer. If what happens to shift workers in the real world is consistent with current findings, this work could eventually be used to develop prevention strategies and drugs that could resolve the error of DNA repair processes. It can also be the basis for strategies to optimize cancer therapy time so that treatment is administered when effectiveness is greatest and side effects are minimal, a procedure called chronotherapy that would need to be adjusted to the internal rhythms of night workers.

“Night workers face considerable health disparities, ranging from increased risk of metabolic and cardiovascular disease to mental disorders and cancer,” said co-author Hans Van Dongen, professor at WSU’s Elson S. Floyd School of Medicine and director of the WSU Sleep and Performance Research Center. “The time has come for us to find diagnostic and treatment solutions for this needy group of essential workers, so that the medical community can face 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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