Role of the Cyclooxygenase Pathway in the Association of Obstructive Sleep Apnea and Cancer.

The objective of this review is to examine the findings that link obstructive sleep apnea (OSA) with cancer and the role played by the cyclooxygenase (COX) pathway in this association. Epidemiological studies in humans suggest a link between OSA and increased cancer incidence and mortality. Studies carried out in animal models have shown that intermittent hypoxia (IH) induces changes in several signaling pathways involved in the regulation of host immunological surveillance that results in tumor establishment and invasion. IH induces the expression of cyclooxygenase 2 (COX-2) that results in an increased synthesis of prostaglandin E2 (PGE). PGE modulates the function of multiple cells involved in immune responses including T lymphocytes, NK cells, dendritic cells, macrophages, and myeloid-derived suppressor cells. In a mouse model blockage of COX-2/PGE abrogated the pro-oncogenic effects of IH. Despite the fact that aspirin inhibits PGE production and prevents the development of cancer, none of the epidemiological studies that investigated the association of OSA and cancer included aspirin use in the analysis. Studies are needed to investigate the regulation of the COX-2/PGE pathway and PGE production in patients with OSA, to better define the role of this axis in the physiopathology of OSA and the potential role of aspirin in preventing the development of cancer.