Dying for a good night of sleep?

Bryn Nelson

Dying for a good night of sleep?

Bryn Nelson

Cancer Cytopathology

visibility

…

description

2 pages

link

1 file

CYTOSource Current Issues for Cytopathology By Bryn Nelson, PhD Edited By David B. Kaminsky, MD, FIAC © THEVISUALSYOUNEED / SHUTTERSTOCK A s researchers work to develop ever-better cancer therapeutics, studies suggest that one of the best may be the easiest to prescribe but often the hardest to obtain: a good night’s rest. Investigators have long suspected that a lack of sleep can exacerbate existing cancers or increase the risk of developing them. Recent studies are solidifying the links and delving into the mechanisms that may help to explain how disrupting the sleep-wake cycle could contribute to a range of malignancies, and how resetting or repairing our inner clock could help to ward them off. However, to capitalize on the momentum, scientists still need to overcome multiple hurdles. One difficulty is understanding which symptoms come first, says Qian Xiao, PhD, MPH, an Cancer Cytopathology May 2019 assistant professor of health and human physiology and epidemiology at the University of Iowa in Iowa City, Iowa. Do more aggressive forms of cancer disrupt patients’ sleep patterns more, or are poor sleepers more susceptible to cancer’s aggression? Either way, she suspects a feedback loop may amplify the effect. Self-reporting of sleep duration poses another challenge, Dr. Xiao says, because it excludes other key aspects of the multidimensional behavior such as quality and regularity. “Most of the studies out there measure sleep via questionnaires, which is not terribly accurate,” Dr. Xiao says. The field, she adds, needs more studies that use objective measurements of sleep such as actigraphy, which uses a sensor similar to an accelerometer, the motion-detecting device found in Fitbits. Patients can wear research-grade Unlocking the Secrets of Sleep The question of how sleep may help to ward off cancer is another area of active investigation. Nighttime rest can be thought of as a period of relative quiescence for the body’s adrenergic 273 Dying for a Good Night of Sleep? Researchers are investigating how poor sleep can increase the risk of cancer or worsen the course of the disease CYTOSOURCE Dying for a Good Night of Sleep? versions of actigraph units on their wrists that record their movements at night and capture better estimates of sleep timing, duration, and quality. David Spiegel, MD, Willson Professor and associate chair of psychiatry and behavioral sciences at Stanford University in Palo Alto, California, is among the researchers taking more comprehensive measurements. In 2014, he and his colleagues published a study in the journal Sleep suggesting that sleep inefficiency—based on multiple awakenings recorded by actigraphy—predicted shorter survival for patients with metastatic breast cancer.1 In a 2016 poster presentation, Dr. Spiegel reported that patients with metastatic colorectal cancer who reported sleeping 7 or fewer hours a day had a 45% higher risk of death within 5 years compared with those who said they slept more hours. The effect was the same regardless of their cancer treatment. “That’s the kind of difference that when you see it with 2 different chemotherapy agents, you get excited, right?” he says. “And the nice thing is this is a treatment you can recommend that has no side effects.” In a 2017 study, also published in the journal Sleep, Dr. Xiao and her colleagues likewise found that higher mortality among patients with colorectal cancer was associated with shorter prediagnosis sleep duration, based on the self-reported number of hours slept per night.2 Although the latter 2 studies used more subjective self-reports than the wrist actigraphy measurements cited in the breast cancer study, all are converging on the same basic story. The take-home message, Dr. Spiegel says, is that some restorative capacity during sleep improves the ability of patients to resist cancer progression, “regardless of what other kinds of treatments are being given and regardless of how you measure the sleep.” nervous system, Dr. Spiegel says. Recent research suggests that such activity can trigger the proliferation of blood vessels that support metastatic disease. In other words, Dr. Spiegel says, “having longer periods of relative adrenergic quiescence can potentially reduce stimulation of the blood supply for tumors.” Other studies have suggested that long-term disruptions of the biological clock, especially in overnight shift workers, can heighten the risk of cancers of the ovary, breast, prostate, and colon. Likewise, scientists have found that manipulating the sleep-wake cycles of mice can encourage cancers to grow faster. One potential mechanism involves the suppression of melatonin, which is believed to have cancer-preventing properties. Levels of the antioxidant hormone normally increase at night and drop in response to light. Shift workers, however, suppress their melatonin overnight and never achieve high levels during the day. A 2018 study in the International Journal of Cancer found no overall association between colorectal cancer risk and rotating night shift work in greater than 190,000 women.3 However, the authors found that the risk of rectal cancer increased significantly among those who had done such shift work for more than 15 years, suggesting a potential role for longterm circadian disruption. Other studies have suggested that circadian rhythm disruption may increase the risk of cancer in flight attendants who fly east-west routes but not north-south routes. For cortisol, a major stress hormone also regulated by circadian rhythms, levels typically peak in the morning, drop throughout the day, and rise again during nighttime sleep until returning to their morning zenith. Dr. Spiegel and other researchers have shown that loss of this normal diurnal variation in cortisol levels likewise predicts long-term cancer progression and mortality. Sleep disruption, they believe, can raise cortisol levels. More stress, as gauged by more cortisone, could deliver a double whammy: stimulating tumor growth and progression while blunting the activity of immune cells that attack transformed and dying cells and help to prevent oncogenesis. To date, researchers have gathered clearer evidence of the role of cortisol in cancer progression rather than in More stress, less sleep, and other factors could help to trigger the growth and metastasis of small incipient tumors. its incidence, but Dr. Spiegel says both areas are being explored. “If these factors can influence progression, it would make sense that they could influence initiation as well,” he says. Could cortisol and melatonin work jointly to affect cancer? “We don’t have all of the pieces of the puzzle assembled, but it certainly makes sense,” he says. Dr. Xiao agrees that cortisol and melatonin levels may influence sleep and tumor development in related ways. “It could be 2 separate pathways that are somehow related but still distinct,” she says. In addition, melatonin has antiestrogen activity that may reduce the risk and improve the prognosis of estrogendependent cancers in women. Linking Sleep and Stress In a study of nearly 43,000 black and white women from 12 southeastern states, Dr. Xiao and her colleagues found that selfreported sleep duration was not associated with the risk of total breast cancer or hormone receptor-positive breast cancer.4 However, the researchers found that black women who reported sleeping fewer than 8 hours per night had a higher risk of estrogen receptor-negative and progesterone receptor-negative breast cancer. The surprising findings, Dr. Xiao says, suggest that errors or biases in the sleep duration reports might mask some associations. Conversely, she adds, the results raise the possibility that an estrogen-independent pathway may link sleep and melatonin levels with breast cancer risk as well. Despite the remaining unknowns, researchers say it is clear that sleep and stress, both of which are risk factors for cancer, are closely intertwined. “One way of managing stress better during the day is to get good sleep at night,” Dr. Spiegel says. “In turn, being stressed tends to disrupt your ability to sleep.” More activity in the body’s stress response systems means less time for the quiescent period of recovery. “Part of the story on cancer is not just generating the tumor, but the tumor’s ability to metastasize and establish a blood supply,” he says. More stress, less sleep, and other factors could help to trigger the growth and metastasis of small incipient tumors. Therefore, from a cancer perspective, sleep could be critical for both prevention and treatment. Western medicine, Dr. Spiegel says, often focuses narrowly on addressing specific medical problems such as cancer, meaning that improved sleep and other lifestyle interventions can get short shrift even though they may have profound effects. “I think part of it is, frankly, an economic problem. Part of it is a problem of the imagination,” he says. “I think we’ve been too focused on the tumor and not enough on the body and system in which the tumor is growing, and they’re 2 parts of the equation. If you want to do the best for patients, you’ve got to do both.” References 1. Palesh O, Aldridge-Gerry A, Zeitzer JM, et al. Actigraphy-measured sleep disruption as a predictor of survival among women with advanced breast cancer. Sleep. 2014;37:837-842. 2. Xiao Q, Arem H, Pfeiffer R, Matthews C. Prediagnosis sleep duration, napping, and mortality among colorectal cancer survivors in a large US cohort. Sleep. 2017;40(4). 3. Papantoniou K, Devore EE, Massa J, et al. Rotating night shift work and colorectal cancer risk in the nurses’ health studies. Int J Cancer. 2018;143:27092717. 4. Xiao Q, Signorello LB, Brinton LA, Cohen SS, Blot WJ, Matthews CE. Sleep duration and breast cancer risk among black and white women. Sleep Med. 2016;20:25-29. DOI: 10.1002/cncy.22142 Content in this section does not reflect any official policy or medical opinion of the American Cancer Society or of the publisher unless otherwise noted. © American Cancer Society, 2019. 274 Cancer Cytopathology May 2019 © GOLUBOVY / SHUTTERSTOCK CYTOSOURCE Dying for a Good Night of Sleep? CONTINUED from previous page

Log In

Dying for a good night of sleep?

Sign up for access to the world's latest research.

Related papers

Related papers

Related topics