Potential Pathophysiological Pathways in the Complex Relationships between OSA and Cancer

SIMPLE SUMMARY: Previous clinical studies have suggested a relationship between obstructive sleep apnea and some types of cancer. This relationship is very heterogeneous, however. This heterogeneity probably depends on the complex pathophysiological pathways activated. It seems that the hypoxia inducible transcription factor, a molecule expressed in situations of hypoxemia such as obstructive sleep apnea, is a key factor. In recent years, however, some new pathophysiological pathways have been shown to be involved, including a large number of biomarkers, pathways related to immune cell dysfunction, exosomes, genetics, and even microbiome alterations. Furthermore, there is an array of tumor cell lines, each with a different capacity to respond to intermittent hypoxia. Both clinical and murine model studies suggest that tumors, such as melanoma and some histological types of breast and lung cancer, could respond in different ways from cancer cell lines in the prostate or the liver. ABSTRACT: Several epidemiological and clinical studies have suggested a relationship between obstructive sleep apnea (OSA) and a higher incidence or severity of cancer. This relationship appears to be dependent on a myriad of factors. These include non-modifiable factors, such as age and gender; and modifiable or preventable factors, such as specific comorbidities (especially obesity), the use of particular treatments, and, above all, the histological type or location of the cancer. Heterogeneity in the relationship between OSA and cancer is also related to the influences of intermittent hypoxemia (a hallmark feature of OSA), among others, on metabolism and the microenvironment of different types of tumoral cells. The hypoxia inducible transcription factor (HIF-1α), a molecule activated and expressed in situations of hypoxemia, seems to be key to enabling a variety of pathophysiological mechanisms that are becoming increasingly better recognized. These mechanisms appear to be operationally involved via alterations in different cellular functions (mainly involving the immune system) and molecular functions, and by inducing modifications in the microbiome. This, in turn, may individually or collectively increase the risk of cancer, which is then, further modulated by the genetic susceptibility of the individual. Here, we provide an updated and brief review of the different pathophysiological pathways that have been identified and could explain the relationship between OSA and cancer. We also identify future challenges that need to be overcome in this intriguing field of research.