Research provides insight into how night shift work increases cancer risk

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 Sciences Spokane.

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

While more research remains to be done, these discoveries could one day be used to help prevent and treat cancer in night shift workers.

“There is growing evidence that cancer is more common in night shift workers, leading the World Health Organization’s International Agency for Research on Cancer to classify night shift work as a likely carcinogen,” said co-corresponding author Shobhan Gaddameedhi, an 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 Environment at North Carolina State University. “It’s unclear, however, why night shift work increases cancer risk, which our research sought to address.”

Studying the rhythms in cancer-related genes

As part of a collaboration 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 PNNL bioinformatics experts to explore the potential involvement of the biological clock, the body clock. built-in mechanism that keeps us 24 hours a day, day and night. 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 includes genes known as clock genes that are rhythmic in their 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 could also be rhythmic, and that night shift work could disrupt the rhythm of these genes.

To test this, they conducted a simulated shiftwork experiment in which 14 participants spent seven days in the WSU Health Sciences Spokane sleep lab. Half of them completed a three-day simulated night shift schedule, while the other half had a three-day simulated day shift schedule. After completing their simulated shifts, all participants were held in a constant routine protocol used to study people’s internally generated biological rhythms independent of external influences. As part of the protocol, they were kept awake for 24 hours in a semi-reclining position under constant light and room temperature exposure and were given identical snacks every hour. Blood was drawn every three hours.

Analyzes of white blood cells taken from the blood samples showed that the rhythm of many of the cancer-related genes was different in the night shift condition than in the day shift condition. In particular, genes related to DNA repair that showed different rhythms in the day shift condition lost their rhythm in the night shift condition.

The researchers then looked at the consequences of the changes in the expression of cancer-related genes. They found that white blood cells isolated from the blood of night shift participants showed more evidence of DNA damage than those of 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 radiated 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 night shift participants were more sensitive to external damage from radiation, a known risk factor for DNA damage and cancer.

“Taken together, these findings suggest that night shift schedules shed the timing of the expression of cancer-related genes in a way that diminishes the effectiveness of the body’s DNA repair processes when they are needed most,” said co-corresponding author Jason McDermott. , a computational scientist in the Biological Sciences Division of the Pacific Northwest National Laboratory.

Potential for improved prevention, treatment

The researchers’ next step is to conduct the same experiment with real shift workers who have consistently worked day or night shifts for many years to determine if, in night workers, the unrepaired DNA damage accumulates over time, which ultimately could increase the risk. of cancer. If what is happening to real shift workers is consistent with current findings, this work could eventually be used to develop prevention strategies and drugs that could address the misjudgment of DNA repair processes. It could also be the basis for strategies to optimize the timing of cancer therapy so that treatment is delivered when the effectiveness is greatest and side effects are minimal, a procedure called chronotherapy that should be tuned to the internal rhythm of cancer. night workers.

“Night shift workers face significant health inequalities, ranging from increased risks of metabolic and cardiovascular disease to mental illness and cancer,” said study co-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 we found diagnostic and treatment solutions for this disadvantaged group of vital 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.