Spokane researchers believe they now have a better idea why night-shift workers are at increased risk of developing certain types of cancer.
Scientists at Washington State University Health Sciences Spokane collaborated with Tri-Cities-based Pacific Northwest National Laboratory on a newly published study. For the first time, the study found that working night shifts can disrupt natural 24-hour rhythms in the activity of certain cancer-related genes.
The study found clues indicating that participants’ white blood cells are more vulnerable to DNA damage among those in simulated night shifts, and their DNA repair mechanisms appear misaligned to deal with damage. The researchers think this finding will help future prevention and cancer treatment.
“It was known the risk for cancer is greater in night-shift workers in particular, but it wasn’t highly clear why this is so,” said Hans Van Dongen, WSU Sleep and Performance Research Center director at the Elson S. Floyd College of Medicine.
Researchers brought people into the lab for about five days total. For the first three days, they were put on simulated shift schedules, with one group following what is normal for day workers while others were on a simulated night-worker schedule for awake hours, then asleep in the daytime.
After the initial days, then all of the participants were put on identical routines for full 24-hour periods in a semi-recumbent position under constants such as the same temperature, lighting and food as small, regular snacks.
That puts natural body rhythms under closer examination with no confounds from sleep or external circumstances, Van Dongen said.
“That turned out to be key,” he said. “When you look under those circumstances, you can start to see there are genes associated with DNA repair, which we all have all the time. DNA needs to be repaired all the time because of free radicals that circulate in our bodies.
“They produce DNA damage, but that normally gets cleaned up by genes that do DNA damage repair. Those genes are known to be really important for preventing cancer. What we saw was it was with night workers where the rhythms of those genes were disrupted.”
The significance is that night workers who are exposed as everybody is to natural sources of DNA damage don’t have that cleaned up in the same way that the day workers have. And there is actually an increase in DNA damage that remains unmitigated, he said.
“That had never been seen before. So we think we’ve found an important mechanism that is the reason and source why night workers are at increased risk for cancer.”
Researchers think that if the DNA damage accumulates over the long run, it can lead to genome instability, which means DNA becomes unstable. When that happens, that’s the first step toward cancer, Van Dongen said.
Understanding that can lead to solutions. It’s not that people need to end night-shift work, he added, because many fulfilling careers include nursing, firefighting, energy work and stints as emergency responders at night.
“Besides, not everyone will end up with cancer, and some people who don’t do night work end up with cancer,” he said.
“Once you know the underlying mechanism and this timing problem with the DNA repair mechanism in the cells of the body, that tells you where to look for solutions.”
That’s two-fold moving ahead.
The first will take some time, but researchers can look for ways to manipulate the rhythms in the cells of those cancer genes that are not turning on at the right time.
“We know what to look at now, so we can start to develop a trajectory to find a solution, maybe finding a driver or other intervention where you fix those rhythms in the cells. That’s a complex and long process.”
When there’s a problem with the timing of genes when they’re most active, it’s something people know how to manipulate, he said. But it’s not simple, and more work is required.
“The basic principles of how you would do that are known. We just didn’t know how to apply this in this population because the underlying problem was never known to begin with,” Van Dongen said.
“Somebody could now with our help start a trajectory to develop a drug that would target those genes precisely and fix this timing so the DNA damage is cleaned up at the right time, and you’re not left with DNA damage that’s not cleaned up.”
The second step is likely to happen quicker, he said, involving cancer treatments and timing for those treatments in light of someone being a night-shift worker.
“We know that those treatments, if they’re timed correctly, can be very effective, and the side effects of those treatments also depend on the timing when you administer them,” Van Dongen said.
“It’s basically keeping an eye on the timing of your treatments so the side effects are minimal and the effectiveness is maximal. We now know in night workers that the timing for those treatments is going to have to be different because their internal rhythms have been disrupted.”
The fact that night workers get cancers more frequently than day workers was already known, he said.
“That was not our discovery. It was just that nobody knew why, so we think we’ve opened up better understanding now. Knowing what the underlying mechanisms are opens up ways to deal with it.”
The group’s next step is to take a closer look at people who have worked as night workers and day workers for a number of years. Such work specifically with Spokane residents might happen in the next year, he said.
“Once we’ve done that, it opens the door to really make a difference in clinical treatments.”
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