Compelling new experimental research has found circadian rhythm disruptions caused by night shift work can alter the expression of tumor-related genes, making one more vulnerable to the DNA damage that leads to cancer. The study builds on a growing understanding of the role circadian rhythms play in our natural DNA repair processes.
In 2019, night shift work was specifically declared “probably carcinogenic to humans” by an independent committee convened by the International Agency for Research on Cancer (IARC). Several years of experimental and observational research had confidently shown night shift workers faced an increased risk of several cancers.
“There has been mounting evidence that cancer is more prevalent in night shift workers, which led the World Health Organization’s International Agency for Research on Cancer to classify night shift work as a probable carcinogenic,” suggests Shobhan Gaddameedhi, co-corresponding author on the new study. “However, it has been unclear why night shift work elevates cancer risk, which our study sought to address.”
Despite prior research finding links between night shift work and a variety of diseases, the mechanisms by which chronic disruptions to one’s circadian rhythm could increase cancer risk were unknown. To investigate this question a team of US researchers recruited 14 healthy volunteers for a comprehensive seven-day laboratory study.
In the sleep lab at Washington State University, half the subjects completed a 72-hour simulated day shift schedule while the other half completed a simulated night shift routine. After the simulation, the participants completed a constant routine protocol in which they were kept awake for 24 hours under consistent light exposure. This part of the protocol is designed to allow investigation of biological rhythms independent of external influences.
“The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways,” the researchers write in the newly published study. “A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule.”
This suggests not only are the expression of certain cancer-related genes directly altered by disrupting circadian rhythms, but night shift schedules seem to negatively influence the body's natural DNA repair processes. Moving to in vivo experiments, the researchers tried to better understand the effect of these gene expression changes on healthy cells.
Investigating white blood cells from the participants, the researchers found greater DNA damage in the night shift subjects. The researchers also exposed white blood cells to ionizing radiation and discovered those cells from the night shift group were much more vulnerable to radiation-induced DNA damage.
“Taken together, these findings suggest that night shift schedules throw off the timing 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,” explains Jason McDermott, co-corresponding author on the study.
As with much scientific research, the new findings raise as many questions as answers. A next step for the researchers will be to investigate real-life night shift workers to see if these findings translate to those who have had circadian disruptions for several years. It’s possible some people’s systems may adapt to this kind of long-term shift work and mitigate these acute changes seen in short-term studies.
It is also suggested the findings could help clinicians better refine cancer treatment protocols, tailoring therapies to an individual patient’s circadian rhythm.
“Night shift workers face considerable health disparities, ranging from increased risks of metabolic and cardiovascular disease to mental health disorders and cancer,” says co-senior author Hans Van Dongen, director of Washington State University’s Sleep and Performance Research Center. “It is high time that we find diagnosis and treatment solutions for this underserved group of essential workers so that the medical community can address their unique health challenges.”
The new study was published in the Journal of Pineal Research.
Source: WSU