Research provides information on how working night shifts increases the risk of cancer

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

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

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

“There has been growing evidence that cancer is more prevalent among night shift workers, which has led the World Health Organization’s International Agency for Research on Cancer to classify night shift work as likely carcinogenic,” said correspondent Shobhan. Gaddameedhi, a former associate professor with the WSU College of Pharmacy and Pharmaceutical Sciences and now with the Department of Biological Sciences at North Carolina State University and the Center for Human Health and the Environment. However, it was not clear why working night shifts increases the risk of cancer, which our study tried to address.

Studying 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 Pacific Northwest National Laboratory (PNNL), Gaddameedhi and other WSU scientists worked with bioinformatics experts at PNNL to study the potential involvement of The built-in biological clock mechanism that keeps us in a night and day cycle of 24 hours. 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 expression, which means that their activity levels vary depending on the time of day or night. The researchers hypothesized that the expression of cancer-associated genes could also be rhythmic and that working night shifts could disrupt the rhythmicity of these genes.

To test this, they performed a simulated shift work experiment that had 14 participants who spent seven days in the sleep lab at WSU Health Sciences Spokane. Half of them completed a three-day simulated night shift program, while the other half were on a three-day simulated day shift program. After the completion of the simulated changes, all participants were kept in a constant routine protocol, which is used to study the biological rhythms generated by humans, independent of any external influence. As part of the protocol, they were kept awake for 24 hours in a semi-inclined position under constant exposure to light and room temperature and were given identical snacks every hour. A blood sample was taken every three hours.

White blood cell tests taken from blood samples showed that the rhythms of many cancer-related genes were different in the night shift state compared to the day shift status. In particular, DNA repair genes that showed distinct rhythms in the daytime state have lost their rhythm in the nighttime state.

The researchers then looked at the consequences of 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 in participants in the day shift. Moreover, after the researchers exposed isolated white blood cells to ionizing radiation at two different times of the day, the cells that were radiated in the evening showed increased DNA damage at night compared to the state in exchange for day. This meant that white blood cells from night shift participants were more vulnerable to external damage caused by radiation, a known risk factor for DNA damage and cancer.

“Taken together, these findings suggest that night shift programs eliminate the timing of the 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 the co-author. -correspondent Jason McDermott, a computer scientist in the Biological Sciences Division of the Pacific Northwest National Laboratory.

Potential for improving prevention, treatment

The next step for researchers is to perform the same experiment with real-world shift workers who have been constantly on day or night shifts for many years to determine whether night workers accumulate unrepaired DNA damage over time, which could eventually increase the risk of cancer. If what is happening to real-world shift workers is consistent with current findings, this work could eventually be used to develop prevention strategies and drugs that could address the wrong DNA repair processes. It could also be the basis for strategies to optimize the timing of cancer therapy so that treatment is given when efficacy is greatest and side effects are minimal, a procedure called chronotherapy that should be adjusted to the internal rhythms of the workers. nightly.

“Night shift workers face considerable health disparities, ranging from increased risk of metabolic and cardiovascular disease to mental health and cancer disorders,” said lead co-author Hans Van Dongen, a professor at Elson College of Medicine. S. Floyd of WSU and director of the WSU Sleep and Performance Research Center. “It’s time to find diagnostic and treatment solutions for this group of essential, well-served workers so that the medical community can address their unique health challenges.”

In addition to 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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