Disruption in DNA repair rhythms may explain higher cancer risk among night-shift workers
Working night shifts may interfere with natural 24-hour rhythms in the activity of certain genes related to cancer, leading to increased cancer risk, according to a study published in the Journal of Pineal Research.
“There is a link that’s being recognized in both human and animal studies between the risk [for] cancer and night work,” Hans P.A. Van Dongen, PhD, director of the Sleep and Performance Research Center and professor at the Elson S. Floyd College of Medicine at Washington State University, said in an interview with Healio. “When you think about night work, you immediately start thinking about the biological clock. The biological clock is the main reason why night work is difficult to do to begin with, and why night-shift workers experience all kinds of problems.”
Van Dongen worked on the study with a team of researchers that included Shobhan Gaddameedhi, PhD, associate professor in the department of biological sciences and toxicology program at the Center for Human Health and the Environment at North Carolina State University.
Van Dongen and Gaddameedhi spoke with Healio about how they approximated night-shift work in their study and measured its effects on genomic DNA, and what their findings may mean for the future of night-shift jobs.
Healio: What prompted you to study the carcinogenic mechanism of night-shift work?
Gaddameedhi: There is evidence that night-shift workers are potentially more prone to various cancers, including breast, colorectal and prostate cancer and some leukemias. We wanted to understand the mechanisms of this for potential cancer prevention, especially among people who have long-term night-shift jobs.
Van Dongen: The two of us initially undertook this study, and then we teamed up with our colleagues at Pacific Northwest National Labs. We needed to come up with a clever way to find out, in the laboratory, how this mechanism might work in shift workers.
We put people on a simulated night-work schedule for 3 days and a control group on a simulated day schedule for 3 days. The work they did during those days was not particularly important, but the schedule was very important. In the night-work schedule, days were flipped by exactly 12 hours. So, night became day and day became night.
Next, we needed to find a way to put these people under circumstances where we could very carefully measure what happened to their biological rhythms. This is called a constant routine protocol. During the 24-hour period of this protocol, we kept all the circumstances in the lab identical, such as light exposure and temperature. Participants were semi-recumbent in a dentist-like chair and kept awake for that period. They got food in 1-hour increments, small snacks that were identical across the 24 hours. So, we created a circumstance where every external influence on the body was completely removed. All you could see were the internal rhythms generated by the body itself. We also took blood samples during that time.
Healio: What did you test the blood samples for?
Gaddameedhi: We wanted to understand how the biological clock disruption and misalignment affects carcinogenic outcomes. We used the 10 hallmarks of cancer and investigated 800 genes that represent these hallmarks and the biological clock. We analyzed white blood cells taken from the blood samples.
Healio: What did you find?
Gaddameedhi: White blood cells taken from those in the night-shift condition showed more DNA damage than those in the day shift. DNA repair genes also lost rhythmicity in the night-work condition.
Van Dongen: The DNA repair pathway in the genes had lost rhythmicity in the night-shift workers. We found that when DNA damage occurs naturally or through external factors, but repair doesn’t occur in the same efficient way at the right times of day, there’s a mistiming between the DNA repair mechanisms and those that cause damage, which could explain the increased DNA damage that we saw. We think that damage accumulates over time, so people who are doing shift work for prolonged periods — months and years on end — would build up a genomic instability, a primary cancer hallmark, which then could lead to cancer.
Healio: Based on your findings, what recommendations would you make to night-shift workers to minimize their risk?
Van Dongen: This is difficult, because shift work is not going to go away. Although shift work comes with several health problems, it also benefits people in terms of the ability to earn a living and work at times that might be convenient to their schedules. It also allows people to do profoundly interesting or rewarding work, such as in hospitals. So, the question then is, what can we tell people to do about it? We’re not quite sure yet, but we think we have a path forward to help people in that situation.
Based on the deeper analysis that Shobhan has done on the samples, we have a reasonably good understanding of how those DNA repair rhythms are supposed to work, as they do in day-shift workers, and how they work in night workers, where the mistiming occurs. Because we know some things about what seems to be going wrong and some of the downstream consequences of that, we think we have a good sense of what we would do if we could develop a treatment to realign those rhythms so we can prevent the formation of that DNA damage or the mistiming in the repair. We’re not close to developing that yet, but we have an idea of how to go about it.
Gaddameedhi: Also, if the rhythms of the genes representing those major cancer pathways are not working properly in night workers, that has consequences if they do develop cancer. We know from other work in cancer that optimal timing of therapeutic interventions, such as chemotherapy, is critical to maximize efficacy of the treatment and minimize the toxicity and side effects that come with it. For night workers, however, that’s going to work differently because their rhythms are out of alignment. We know about the basic principle of the timing of treatments; it’s called chronotherapy. We now need to adjust it to night work. That’s not the same as preventing cancer, but it’s a step forward.
Healio: What further research do you plan to conduct on this topic?
Van Dongen: We have studied this in healthy young adults who were not necessarily night-shift workers. If you have been a shift worker for months and years on end, your body may have developed additional mechanisms that either provide some resilience or make it worse. So, in a seasoned shift worker, these mechanisms may be slightly — or even quite significantly — different. The first thing we need to do is look at actual shift workers who have been in their profession for a while, and make sure that what we found in our research volunteers holds true.
Gaddameedhi: As Hans said, night-shift work cannot be stopped or avoided; emergency workers do night shifts, as do police officers. Findings have indicated that especially in terms of endogenous DNA damage, this damage potentially could come from oxidative stress. There is literature that shows oxidative stress can be minimized by consuming foods and fluids that are rich in antioxidants. So, one thing we can do is recommend that individuals who are performing shift work maintain a healthy diet that is rich in antioxidants.
For more information:
Shobhan Gaddameedhi, PhD, can be reached at Department of Biological Sciences and Toxicology Program, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695; email: sgaddam4@ncsu.edu
Hans P.A. Van Dongen, PhD, can be reached at Suite 702, Center for Clinical Research and Simulation, Washington State University Health Sciences Spokane, 412 E. Spokane Falls Blvd., Spokane, WA 99202-2131; email: hvd@wsu.edu.
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