Stanford Research Builds Link Between Sleep, Cancer Progression

Previous studies have found people with cancer who go through group therapy or have a strong social network fare better than those with weaker social support. The question has been how psychosocial factors exert their influence on cancer cells. David Spiegel, MD, the Jack, Lulu and Sam Willson Professor in the School of Medicine, and Sandra Sephton, PhD, Spiegel's former postdoctoral fellow now at the University of Louisville School of Medicine, suggest that a person's sleep/wake cycle might be the connection. Their work will be published in the October issue of Brain, Behavior, and Immunity.

"Psychosocial factors affect your behavior patterns, such as exercise, what you eat and drink, and your sleep," Spiegel said. Of these factors, how well you sleep can seriously alter the balance of hormones in your body. This makes the sleep/wake cycle, also called the circadian rhythm, a good candidate for linking a person's social network to their cancer prognosis.

Spiegel suggested two possible ways in which the circadian rhythm may influence cancer progression. The first involves a hormone called melatonin, which the brain churns out during sleep. Melatonin belongs to a class of compounds called anti-oxidants that mop up damaging free-radical compounds. With a disrupted circadian rhythm, the body produces less melatonin and the cell's DNA may be more prone to cancer-causing mutations.

Melatonin also slows the ovaries' production of estrogen. For many ovarian and breast tumors, estrogen spurs the cancerous cells to continue dividing. Shift workers who work through the night and produce less melatonin may therefore produce more cancer-activating estrogen, the researchers said.

The second link lies with a hormone called cortisol, which normally reaches peak levels at dawn then declines throughout the day. Cortisol is one of many hormones that help regulate immune system activity, including the activity of a group of immune cells called natural-killer cells that help the body battle cancer.

One study found that people who are at high risk of breast cancer have a shifted cortisol rhythm, suggesting that people whose cortisol cycle is thrown off by troubled sleep may also be more cancer-prone. In past work, Spiegel and his coworkers have found that women with breast cancer whose normal cortisol cycle is disrupted - with peak levels in the afternoon rather than at dawn - die earlier from the disease. Those women whose cortisol cycle was shifted also tended to sleep poorly, have lost a spouse or partner and have cancer-fighting branches of the immune system suppressed.

Other studies back up this theorized connection. Spiegel cited the recent finding that night-shift workers have a higher rate of breast cancer than women who sleep normal hours. What's more, mice whose circadian rhythm has been interrupted show much more rapid tumor growth than normal mice. Together, these studies led Spiegel to suspect that a poor night's sleep may be one link between a weak social network and a poorer cancer prognosis.

Spiegel said that although much remains to be learned about how the stress response system affects tumor growth, the current research draws a connection that doctors should heed. "I'd like people to reconceptualize cancer as a biological event that triggers stress responses affecting how the disease progresses," he said. Managing those stress responses by adopting healthy eating and exercise habits, getting a good night's sleep, and finding good emotional and social support, should be regarded as much a part of cancer treatment as chemotherapy or radiation, he said.

"Doctors should not just be fighting the tumor but helping the people with the disease to live with it," he said.

Stanford has a Cancer Supportive Care Program, directed by Spiegel, UC-San Francisco oncologist Ernest Rosenbaum, MD, and nurse Holly Gautier, that offers yoga, counseling, energy healing and other stress reduction classes for people with cancer. Spiegel said these types of services can help people with cancer maintain their emotional well- being, which could in turn help them sleep well and perhaps help their bodies better resist cancer growth.

"Although having cancer might be something to lose sleep over," Spiegel noted, "we'd rather help people regain the sleep and lose the cancer."

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Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.