title: Obstructive sleep apnea and cancer: Epidemiologic links and theoretical biological constructs.
abstract: Sleep disorders have emerged as highly prevalent conditions in the last 50-75 y. Along with improved understanding of such disorders, the realization that perturbations in sleep architecture and continuity may initiate, exacerbate or modulate the phenotypic expression of multiple diseases including cancer has gained increased attention. Furthermore, the intermittent hypoxia that is attendant to sleep disordered breathing, has recently been implicated in increased incidence and more adverse prognosis of cancer. The unifying conceptual framework linking these associations proposes that increased sympathetic activity and/or alterations in immune function, particularly affecting innate immune cellular populations, underlie the deleterious effects of sleep disorders on tumor biology. In this review, the epidemiological evidence linking disrupted sleep and intermittent hypoxia to oncological outcomes, and the potential biological underpinnings of such associations as illustrated by experimental murine models will be critically appraised. The overarching conclusion appears supportive in the formulation of an hypothetical framework, in which fragmented sleep and intermittent hypoxia may promote changes in multiple signalosomes and transcription factors that can not only initiate malignant transformation, but will also alter the tumor microenvironment, disrupt immunosurveillance, and thus hasten tumor proliferation and increase local and metastatic invasion. Future bench-based experimental studies as well as carefully conducted and controlled clinical epidemiological studies appear justified for further exploration of these hypotheses.
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL, USA. Electronic address: dgozal@uchicago.edu.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-IDIBAPS, Barcelona, Spain; CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
authors.affiliation: Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Nieto
mesh_terms: D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000150:complications; D007249:Inflammation; D051379:Mice; D009369:Neoplasms / Q000209:etiology*; D020181:Sleep Apnea, Obstructive / Q000150:complications*
keywords: Cancer; Inflammation; Intermittent hypoxia; Sleep apnea; Sleep deprivation; Tumor-associated macrophages