Photo by Robert Hood / Fred Hutch News Service
In 2006, just a year after graduating from nursing school, Nancy Krupienski took a position as a night nurse at a hospital near her home in Vernon, Connecticut. She worked 11 p.m. until 7 a.m. so she and her husband, who worked days, could grow their family and save on day care costs. Her sleep suffered “considerably” but the 31-year-old stuck it out, doing her best to catch up on sleep during her days off.
Three years and two babies later, her sleep was still bad — and so was her health, especially after her oldest child started school and began bringing home germs.
“I started getting sick,” said Krupienski, rattling off a host of ailments including respiratory infections, sinus infections, chronic stomach problems, acid reflux, gall bladder issues and more. “I could not catch a break.”
In 2014, Krupienski left nursing — and her onerous night shift — for a less stressful job at a high school. Her sleep returned to normal and her health improved dramatically. Then in November 2016, she learned she had breast cancer, a diagnosis that left her with a nagging suspicion.
“I always wonder if some sort of cell confusion occurs with night shift, reduced immunity and lack of sleep which could've had some sort of influence on me getting cancer,” said Krupienski, now 42. “I think my body was so worn out from so many years of lackluster sleep. Perhaps it triggered something that triggered the cancer.”
Photo courtesy of Nancy Krupienski
Most of us know that getting enough sleep is crucial for our health. Sleeping seven to nine hours a night keeps the body in good working order. Sleep too little or too sporadically for too long and you could fall prey to anything from diabetes to depression to cardiovascular disease.
But it’s not just about how much you sleep. It’s also important when you sleep.
A 2001 study by Fred Hutchinson Cancer Research Center epidemiologist Dr. Scott Davis found nurses like Krupienski, who regularly worked a graveyard shift, were more than 1.5 times more likely to get breast cancer. And other studies have backed up the night shift–cancer connection, leading the International Agency for Research on Cancer in 2007 to classify shift work that disrupts circadian rhythm as “probably carcinogenic to humans.”
Why, exactly, is working at night so bad for our health?
For the past few years, Fred Hutch epidemiologist Dr. Parveen Bhatti has been trying to figure that out. His latest study, published today in the journal Occupational and Environmental Medicine, confirms that the body repairs DNA damage more efficiently if you sleep during the night than it does if you sleep during the day — and offers insights as to why.
Apparently, Ray Charles was right. The night time is the right time — for sleep, at least.
The night work–cancer connection
An epidemiologist who came to Fred Hutch from the National Cancer Institute in 2009, Bhatti is the first to admit the night work–cancer question is fraught with complications.
“Shift work is a really complex exposure,” he said. “There’s light at night. There’s sleep disruption. There are different types of shift schedules that one can have.”
And there are also conflicting findings.
Last year, a large British prospective study compared breast cancer incidence with shift-work data from England’s Million Women Study and concluded there was no night work–breast cancer connection, after all. Among other problems (the study relied on participants’ memory of how much shift work they’d done over the decades), Bhatti believes the study’s three-year follow-up was “way too short” to support this conclusion.
“Studies like the one out of the U.K. try to close the door,” he said. “I feel we have a lot more to learn and there might be people we really need to help,” referring to the millions of people around the world who work nights and, as a result, might be at risk for cancer and other diseases.
To get to the bottom of whether night work could actually drive cancer, Bhatti turned to the molecular data from night shift workers, focusing on a common biological marker of DNA damage that’s been connected to disease.
For a 2016 study, Bhatti and his team used previously stored urine specimens collected during day sleep and night sleep from a group of 223 Seattle-area nurses, orderlies and other hospital employees who regularly pulled graveyard shifts. The researchers compared levels of DNA damage between the day sleep and night sleep specimens. For the current study, he used banked urine specimens collected during night work from 50 of those participants, then compared night work to night sleep DNA damage levels to see what tale the specimens had to tell.
In normal cellular metabolism, our bodies produce something called reactive oxygen species which react with DNA to cause mutations. One such DNA injury is known as 8-OH-dG, or 8-hydroxydeoxyguanosine, which, Bhatti said, “sits in your DNA and, if it’s not repaired, can cause a mutation that can lead to cancer.”
“Your repair machinery cuts out that damage and it’s actually excreted in urine so we can measure the repaired damage in urine,” he said. “In our studies, that’s what this marker seems to have captured — repair.”
In other words, people with high levels of 8-OH-dG in their urine might be benefitting from their body’s DNA repair machinery. People with low levels of the biomarker in their urine, not so much.
What’s driving the damage?
Bhatti’s 2016 study of night shift workers found those who slept during the day had low levels of 8-OH-dG in their urine. Their DNA was not being repaired.
“The damage was done but it wasn’t repaired,” said Bhatti. “It’s sitting in their cells.”
His most recent study also confirmed that night shift workers had a reduced ability to repair DNA damage due to a connection between circulating melatonin levels — notoriously low in night shift workers — and the body’s ability to repair DNA damage.
Lower levels of melatonin were associated with lower levels of 8-OH-dG. Bhatti's latest study confirmed this association.
As most people know, the hormone melatonin is a chemical messenger that comes out at night, much like the moon. It’s even been called the “hormone of darkness,” since melatonin levels are normally low during the day. We’re all built a little differently, but usually, our level of melatonin starts to rise around 7 or 8 p.m., peaks at about 1 or 2 in the morning, then drops off as we near our wake-up time.
Exposure to light cues the pineal gland, tucked in middle of the brain, to make less melatonin. That’s why we’re often told to keep electronic devices out of the bedroom: the blue wavelengths of light emitted by many laptops and phones suppress melatonin the most.
Melatonin’s main function is synchronizing the physiology and rhythms of the body — sort of like the moon affects the tides — but it is also, Bhatti found, tied to the repair of DNA damage.
“What seems to be happening, and this is supported by a lot of animal and cellular evidence, is melatonin normally drives repair of damage,” Bhatti said. “So with low levels of melatonin, their repair machinery isn’t functioning at optimal levels.”
What does this mean for the 15 million or so people in the U.S. who work night shifts?
Bhatti said our society will never get rid of its night shifts, but there may be workarounds as far as “figuring out what we can do to make life better for shift workers and improve their long-term health.”
Toward that end, he wants to conduct a new study that will look at melatonin supplementation in night workers.
“We’ll give them melatonin supplements to see what the effects are on the DNA damage marker,” he said. “Melatonin could really help and be an easy fix.”
But it’s unproven for now, he warned.
“It’s important that shift workers don’t go out and automatically start taking melatonin,” he said. “It’s not standardized, it’s not FDA-regulated and there are different formulations out there. It’s difficult to know what fillers are included with the melatonin. And we haven’t done enough work yet to see if there are any negative consequences of taking it.”
Bhatti said there are “a lot of misunderstandings” about how melatonin even works.
“People think it’s a sedative but it actually promotes sleep when it’s supposed to happen — at night,” he said. “There have been studies done where they’ll inject people with huge quantities of melatonin during the day and it will have no effect on their sleepiness.”
Krupienski, the nurse who wondered if night work and sleeplessness contributed to her breast cancer, said she tried melatonin, as well as valerian root, Benadryl and Unisom in an effort to sleep during the day, but nothing worked.
“Sleep agents did not help,” said Krupienski, who is currently undergoing radiation and hormone treatment for her breast cancer. “I believe the chronic sleeplessness was a constant strain on my immune system. Obviously, many people work nights and never get cancer.”
If his next grant application is approved, Bhatti plans to give shift workers melatonin supplements and then track the effects on DNA damage, sleepiness, alertness, overall health and more.
Until that data is available, he said shift workers should be mindful of their health, proactively working towards counteracting any increased risks of cancer from working graveyard shifts.
“It’s even more critical for them to pay attention to public health messages about healthy lifestyle — getting good sleep, eating a proper diet, exercising, all of those things,” he said. “They may be more at risk from working at night. You want to do what you can to balance against that.”
Diane Mapes is a staff writer at Fred Hutchinson Cancer Research Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she blogs at doublewhammied.com and tweets @double_whammied. Email her at firstname.lastname@example.org.
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