Sleep disorders have been linked to cancer incidence. A new study investigates how the duration and severity of the sleep disturbance impact that risk.

Interview by Alyx Arnett

As evidence mounts linking sleep disturbances with increased cancer risk, a new study delves into how the severity and duration of sleep disorders might influence this relationship.

Utilizing de-identified data spanning from 1999 to 2010 and involving 663,869 veterans in the southeastern United States, researchers investigated the impacts of sleep disorders on the likelihood of developing prostate, breast, colorectal, and other cancers.

This retrospective cohort study is distinct in its approach to not only confirming the association between sleep disorders and cancer but also dissecting how prolonged exposure to poor sleep quality and more severe manifestations of sleep disorders could escalate risks. The study also explores racial disparities.

Study author James Burch, PhD, discussed this study with Sleep Review via email.

[Editor’s Note: Read the study, “Sleep disorders and cancer incidence: examining duration and severity of diagnosis among veterans,” in Frontiers in Oncology.]

What inspired the focus on this topic?

Sleep disruption can activate several pathological processes related to carcinogenesis, including inflammation, oxidative stress, changes in DNA methylation, endocrine dysregulation (eg, altered secretion of melatonin, which has “oncostatic” properties), and altered circadian rhythms (including the expression of clock genes, which regulate the expression of thousands of “clock-controlled genes” including oncogenes and tumor suppressors). I’ve had a long-standing interest in circadian processes and how they relate to disease and health.

What were your main findings?

Patients with and without a sleep disorder were followed for an average of 11 years, and those with sleep disorders had increased cancer risks. The results are generally consistent with other studies of cancer risk in populations not only with sleep disorders like sleep apnea or insomnia but also other sleep problems that were measured using questionnaires or with short-term quantitative sleep measures such as wrist actigraphy.

This study is a bit different from prior research because it tested whether patients with more severe or longer-duration diagnoses had greater cancer risks relative to those without such characteristics. We found that patients with a longer duration or greater severity of sleep disorder had the greatest risks.

For sleep disorder severity, we used a surrogate or proxy measure, the number of sleep-related treatments in their medical record. It’s important to note that there may be alternative explanations than this being an indicator of severity, and we discuss those in the paper.

This study also contributed to the existing literature by examining whether there are racial disparities in the relationship between sleep disorders and cancer incidence. We found that African American patients with more sleep-related treatments (ie, greater severity) had greater risks relative to those in other race groups or with fewer treatments.

Were there any surprising findings?

The disparity between African American and European American patients was somewhat unexpected. Because the population was all veterans, one would expect everyone to receive equal care. However, we also cited one study that reported higher rates of gastric, hepatic, and prostatic cancer in veteran African Americans relative to European American veterans. On average, African Americans also tend to have worse sleep than European Americans. We discuss several possible explanations for the racial cancer disparities that we and others have observed, including the possible role of discrimination and chronic stress.

Your study highlights the increased cancer risk with longer durations and greater severity of sleep disorders. Can you discuss the potential biological or physiological mechanisms that might explain this relationship?

There is a compelling body of evidence indicating that sleep problems tend to be persistent. Most tumors take years—if not a decade or more—to develop, so our observation that risks tended to increase with increasing duration of sleep disorder diagnosis is an important and novel finding that suggests a form of dose-response with persistent sleep disruption.

The basic mechanisms of carcinogenesis are still being worked out by molecular biologists, but the classical paradigm is one of initiation, promotion, and progression. Initiation refers to sentinel DNA mutations that drive the formation of other mutations (or epigenetic lesions), and then key cellular processes that typically keep normal cell growth in check are disrupted, which eventually leads to genomic instability and unrestricted cell growth that can manifest as a tumor.

Clock genes and melatonin are molecules that can prevent or restrict tumor growth, and the action of these agents can be compromised by sleep disturbances.

Another possible process that is involved is chronic stress. Sleep disruption causes stress, and stress causes inflammation, which is a cancer risk factor. Physiological systems are complex, and cancer is a multi-stage, multifactorial disease. The critical molecular and physiological processes that drive the relationship between sleep disturbances and cancer remain to be determined.

What are the clinical implications?

Although a few inconsistencies and uncertainties remain, there is now a fairly substantial weight of evidence documenting a linkage between sleep disruption and cancer. The latency between initiation of sleep disturbances and eventual tumor formation may be a decade or more, which has important clinical implications and introduces a window of opportunity for prevention.

What role do you see for sleep medicine specialists in integrating the insights from your study into multidisciplinary cancer prevention efforts?

Several promising treatments are mentioned in our paper. One of these is supplemental use of melatonin, which can promote sleep and also has antiproliferative, antioxidant, immune enhancing, and anti-inflammatory properties, although it has not been thoroughly studied for cancer prevention.

Compounds that act upon the orexin (hypocretin) receptor system can be used to treat insomnia and can also inhibit tumor growth. Vitamin D is another natural compound that can inhibit tumor growth, and deficiencies in vitamin D are associated with poor sleep quality and sleep disorders. Other potential treatments may act upon the autonomic nervous system, which can reduce stress and inflammation as well as improve sleep.

What future research should be done?

Our study results suggest that optimal sleep and appropriate sleep disorder management may represent modifiable risk factors for facilitating cancer prevention. It would be great to see more studies focusing on sleep disorder treatments that are safe, effective, sustainable, and low-cost that are designed to investigate whether sleep improvement can effectively prevent cancer, which would add to the long list of sleep’s beneficial properties.

Research is needed to work out appropriate dosages (timing, frequency, intensity) of the more promising sleep-promoting, cancer prevention therapies.