Research offers insight into how night work increases cancer risk

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

Posted online in Journal of Pineal Research, the study involved a controlled laboratory experiment that used healthy volunteers who were on simulated night or day shifts. Study results suggest that night shifts disrupt the natural 24-hour rhythms in the activity of certain cancer-related genes, making night workers more vulnerable to DNA damage while causing shift timing errors. DNA repair mechanisms of the body. deal with this damage.

While more research is still needed, these findings could one day be used to help prevent and treat cancer in night workers.

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

Study of rhythms in genes linked to cancer

In a partnership between the WSU Sleep and Performance Research Center and the US Department of Energy’s Pacific Northwest National Laboratory (PNNL), Gaddameedhi and other WSU scientists worked with PNNL bioinformatics experts to study the potential involvement of the body clock built-in mechanism that keeps us on a 24-hour day-to-night cycle. Although there is a central body 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 their expression, which means their activity levels 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 work could disrupt the rhythmicity of these genes.

To test this, they conducted a mock shift work experiment that took 14 participants to spend seven days in the sleep lab at WSU Health Sciences Spokane. Half of them followed a simulated three-day night shift schedule, while the other half followed a simulated three-day day shift schedule. After completing their simulated changes, all participants were kept in a constant routine protocol which is used to study the biological rhythms generated internally by humans independent of any external influences. As part of the protocol, they were kept awake for 24 hours in a semi-reclining posture under constant exposure to light and room temperature and given identical snacks every hour. Every three hours, a blood sample was taken.

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

The researchers then looked at the consequences of changes in gene expression linked to cancer. They found that white blood cells isolated from the blood of night shift participants showed more signs of DNA damage than those of day shift participants. Additionally, after researchers exposed isolated white blood cells to ionizing radiation at two different times of the day, cells that were radiated at night showed increased DNA damage in the nighttime condition compared to at the day condition. This meant that the white blood cells of the participants on the night shift were more vulnerable to external damage from radiation, a known risk factor for DNA damage and cancer.

“Taken together, these results suggest that night shifts alter the timing of cancer-related gene expression in a way that reduces the efficiency of the body’s DNA repair processes when they are on. most needed, ”said co-correspondent author Jason McDermott, a computer scientist in the Division of Biological Sciences at the Pacific Northwest National Laboratory.

Potential for improvement in prevention and treatment

The researchers’ next step is to conduct the same experiment with real-world shift workers who have been doing regular day or night shifts for many years to determine whether in night workers the unrepaired DNA damage is occurring. build up over time, which could ultimately increase the risk. cancer. If what is happening with shiftworkers in the real world is consistent with current findings, this work could potentially be used to develop prevention strategies and drugs that could address poor timing in DNA repair processes. It could also serve as the basis for strategies to optimize the cancer treatment schedule so that treatment is given when effectiveness is greatest and side effects are minimal, a procedure called chronotherapy that should be adapted to the rhythms. internal night workers.

“Night workers face huge health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” said co-lead author Hans Van Dongen, WSU professor Elson S. Floyd College of Medicine and Director of the WSU Center for Sleep and Performance Research. “It is high time that we find diagnostic and treatment solutions for this underserved group of essential workers so that the medical community can meet its unique health challenges.”

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

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Funding: National Institutes of Health, Congress-led medical research programs, BRAVE investment in the Pacific Northwest National Laboratory