Putative Links Between Sleep Apnea and Cancer: From Hypotheses to Evolving Evidence

Abstract

In recent years, the potentially adverse role of sleep-disordered breathing in cancer incidence and outcomes has emerged. In parallel, animal models of intermittent hypoxia (IH) and sleep fragmentation (SF) emulating the two major components of OSA have lent support to the notion that OSA may enhance the proliferative and invasive properties of solid tumors. Based on several lines of evidence, we propose that OSA-induced increases in sympathetic outflow and alterations in immune function are critically involved in modifying oncologic processes including angiogenesis. In this context, we suggest that OSA, via IH (and potentially SF), promotes changes in several signaling pathways and transcription factors that coordinate malignant transformation and expansion, disrupts host immunologic surveillance, and consequently leads to increased probability of oncogenesis, accelerated tumor proliferation, and invasion, ultimately resulting in adverse outcomes.

Figure 1 –

Theoretical framework of possible mechanisms by which sleep fragmentation or intermittent hypoxia in the context of OSA may not only lead to maladaptive transcriptional regulation, potentially affecting malignant transformation potential, but also disrupt sympathetic outflow and alter multiple immunoregulatory cellular targets that in turn will impose changes in the oncogenic properties of the tumor (eg, vessel formation, invasiveness, proliferation).