SLEEP, CIRCADIAN RHYTHMS, AND LUNG CANCER.

Abstract

Lung cancer is the leading cause of cancer-related mortality worldwide, with the prevalence of the disease continually rising. Therefore, identifying disease-modifying risk factors is critical, with increasing recognition of the impact of sleep quality/sleep disorders. This narrative review summarizes the evidence on the role of five domains of sleep on lung cancer incidence and progression: (i) sleep quality/duration, (ii) sleep disordered breathing, (iii) circadian rhythm disturbances, (iv) sleep-related movement disorders and (v) personal, environmental and social factors that modulate each of these associations. Epidemiological evidence supports reduced sleep duration, increased sleep duration, poor sleep quality, insomnia, obstructive sleep apnea, evening chronotype, peripheral limb movements in sleep, and less robustly for night shift work and restless leg syndrome to be associated with increased risk of lung cancer development, with potential impacts on cancer survival outcomes. Proposed mechanisms underlying the biological plausibility of these epidemiological associations are also explored, with common theories relating to immune dysregulation, metabolic alterations, reductions in melatonin, sympathetic overactivation, increased reactive oxygen species, production of protumorigenic exosomes and inflammation. We also summarized potential treatments addressing impaired sleep quality/sleep disorders and their ability to attenuate the risk of lung cancer and cancer survival. While evidence on reversibility is inconsistent, there are trends toward positive outcomes. Future research should focus on clinical trials to confirm cause and effect relationships, large epidemiologic studies for incidence/prognosis, clarification on the relative efficacy of treatment modalities, and more in vivo animal models to establish the molecular mechanisms underlying these relationships.