May 25, 2012 (San Francisco, California) — In a study that followed more than 1500 state employees in Wisconsin for more than 20 years, sleep apnea — particularly if it was severe — was found to be associated with a greatly increased risk for death from cancer, researchers reported here at the American Thoracic Society 2012 International Conference.

In the study, those with severe sleep apnea had a relative risk for cancer mortality of 4.8 (95% confidence interval, 1.7 to 13.2; P = .0052) when the researchers used the apnea-hypopnea index to classify sleep-disordered breathing. When the researchers calculated hypoxemia index (the percent of time below 90% oxyhemoglobin saturation), the relative risk for cancer mortality ranged from 2.9 for those with moderate sleep apnea to 8.6 for those with severe sleep apnea.

“This is the first study to show that sleep apnea is related to increased risk of cancer death,” said lead researcher F. Javier Nieto, MD, PhD, chair of the Department of Population Health Sciences at the University of Wisconsin School of Medicine and Public Health in Madison.  Chronic hypoxia, or inadequate supply of oxygen, has been associated with both therapeutic resistance to cancer therapies and tumor progression in laboratory studies, so these findings make sense, the researchers explain.

Of the 1522 state employees assessed in the study, 365 (24%) had at least mild sleep apnea and 59 (4%) had severe sleep apnea. The researchers included 9 subjects who used continuous positive air pressure (CPAP) machines — a common sleep apnea treatment — in their analysis. They noted that the use of CPAP was most likely an indication of recent sleep apnea. The association between sleep apnea and cancer death remained when the researchers removed those treated with CPAP.

Subjects completed questionnaires on educational level, general health, physical activity, body mass index, diabetes diagnoses, and daytime sleepiness. The link between increased risk for cancer death and sleep apnea was independent of obesity and daytime sleepiness, they note. After 22 years of follow-up, there were 112 deaths in the Wisconsin cohort, 50 of which could be attributed to cancer, Dr. Nieto said. The most common cause of cancer death was lung cancer, but deaths were also attributed to colorectal, endometrial, ovarian, brain, breast, bladder, and liver cancer.  In the cohort, 31 cancer deaths occurred in those without sleep apnea and 19 in those with mild, moderate, or severe sleep apnea.

“The next step in our research is to find out whether sleep apnea increases the risk for cancer or whether the problem is that when you have apnea and are diagnosed with cancer, your survival is less certain,” Dr. Nieto said.

Dr. Nieto noted that it is possible that CPAP treatment ameliorates the risk for cancer or cancer death, but it is unlikely that this hypothesis would ever be tested. “It would be unethical to do such a study because withholding CPAP treatment would subject you to a range of health risks, including falling asleep while driving,” he said.  “This study on sleep apnea and cancer mortality is very intriguing,” said Clete Kushida, MD, PhD, professor and medical director of the Stanford Sleep Medicine Center in Palo Alto, California.  However, in addition to the small number of cancer cases, this study might have been limited by the fact that the researchers did not look at the impact of sleep quality, Dr. Kushida noted. “Is it really the hypoxia, or is it the disruption in sleep quality that is a risk factor for cancer death?” he asked. “When your sleep is disrupted, it results in sleep deprivation, and that can be a significant stressor on the body,” he said.

“The bottom line is that we need more studies and further analyses,” Dr. Kushida said.

The study was funded by the National Heart, Lung, and Blood Institute. Dr. Nieto and Dr. Kushida have disclosed no relevant financial relationships.

American Thoracic Society (ATS) 2012 International Conference: Abstract 30627. Presented May 20, 2012.
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