Sleep Disruption and Cancer: Chicken or the Egg?

Abstract

Sleep is a nearly ubiquitous phenomenon across the phylogenetic tree, highlighting its essential role in ensuring fitness across evolutionary time. Consequently, chronic disruption of the duration, timing, or structure of sleep can cause widespread problems in multiple physiological systems, including those that regulate energy balance, immune function, and cognitive capacity, among others. Many, if not all these systems, become altered throughout the course of cancer initiation, growth, metastatic spread, treatment, and recurrence. Recent work has demonstrated how changes in sleep influence the development of chronic diseases, including cancer, in both humans and animal models. A common finding is that for some cancers (e.g., breast), chronic disruption of sleep/wake states prior to disease onset is associated with an increased risk for cancer development. Additionally, sleep disruption after cancer initiation is often associated with worse outcomes. Recently, evidence suggesting that cancer itself can affect neuronal circuits controlling sleep and wakefulness has accumulated. Patients with cancer often report difficulty falling asleep, difficulty staying asleep, and severe fatigue, during and even years after treatment. In addition to the psychological stress associated with cancer, cancer itself may alter sleep homeostasis through changes to host physiology and via currently undefined mechanisms. Moreover, cancer treatments (e.g., chemotherapy, radiation, hormonal, and surgical) may further worsen sleep problems through complex biological processes yet to be fully understood. This results in a “chicken or the egg” phenomenon, where it is unclear whether sleep disruption promotes cancer or cancer reciprocally disrupts sleep. This review will discuss existing evidence for both hypotheses and present a framework through which the interactions between sleep and cancer can be dissociated and causally investigated.

Risk-Reducing Measures for Cancer Prevention

“…It is also actively involved in the sleep and wake pattern; reproductive cycles in humans are usually diminished through long-term exposure to high artificial light during late-night working hours, which increases the risk of cancer, especially breast cancer [ 66 ]. Sleep alteration, disturbances, and other sleep problems are common in patients after a cancer diagnosis, which is associated with severe outcomes of the disease [ 67 ]. This is usually due to the numerous physiological and biological changes in the body due to cancer, and various treatments such as radiation therapy, surgery, hormonal therapy, and chemotherapy initiated to tackle the disease [ 67 ].…”

“…66) Sleep alteration, disturbances, and other sleep problems are common in patients after a cancer diagnosis, which is associated with severe outcomes of the disease. 67) This is usually due to the numerous physiological and biological changes in the body due to cancer, and various treatments such as radiation therapy, surgery, hormonal therapy, and chemotherapy initiated to tackle the disease. 67) The normal duration of sleep in an individual varies due to different factors such as the physiological and health components of an individual.…”

“…67) This is usually due to the numerous physiological and biological changes in the body due to cancer, and various treatments such as radiation therapy, surgery, hormonal therapy, and chemotherapy initiated to tackle the disease. 67) The normal duration of sleep in an individual varies due to different factors such as the physiological and health components of an individual. 68) Thus, sleep recommendation is usually on an individual-toindividual basis, and it is imperative to adopt and adapt to an individual's given sleep recommendations by medical personnel which incorporates the time of sleep and measures to ensure sleep quality.…”

Integrative Approaches to the Treatment of Cancer

“…A meta-analysis conducted by Shi et al [ 77 ] of these 8 studies found there was a modest 24% increased risk of cancer in those with insomnia (compared to those without insomnia). A recent review by Berisha and colleagues [ 86 ] indicates that chronic disruption of sleep/wake states prior to disease onset is associated with an increased risk of some cancers, e.g., breast, and that sleep disruption after cancer onset is often associated with poorer outcomes.…”

“…As described by Shi et al [ 77 ], other potential mechanisms of action proposed to explain how insomnia may contribute to cancer include dysregulation of melatonin [ 89 ] and circadian rhythm/chrono- disruptions (which can affect rhythmicity in neuroendocrine and immune parameters) [ 90 ], dysregulation of genes involved in tumour suppression [ 91 ], involvement of the oestrogen-signalling pathway [ 92 ], impaired immune function [ 93 ] and inflammation [ 94 ]. See Berisha et al [ 86 ] and Shi et al [ 77 ] for further discussion.…”