Original ArticleObstructive sleep apnea is associated with cancer mortality in younger patients
Introduction
Obstructive sleep apnea (OSA) is characterized by repetitive episodes of partial or total obstruction of airflow, causing intermittent oxygen desaturation and sleep disruption [1], [2], [3], [4], [5], [6], [7], [8]. Intermittent hypoxia (IH) is a hallmark of OSA severity and results in considerable injury at cell level [9]. IH has been associated with the overexpression of oxidative stress and inflammatory transcription factors, which are potentially involved in de-novo carcinogenesis, accelerated tumor growth, and increased resistance to treatments [9], [10], [11], [12], [13], [14]. It is therefore biologically plausible to anticipate an association between OSA and cancer incidence and mortality [15], [16]. Accordingly, Almendros et al. recently observed in an animal model of melanoma that mice subjected to an IH pattern mimicking OSA presented increased tumor growth rate [17] and metastasis to the lung [18], compared with normoxic controls. Along the same lines, our research group has recently reported greater cancer incidence in OSA patients with increased overnight hypoxia [19].
The only study that has previously addressed the association between OSA and cancer mortality in humans is based on the analysis of the Wisconsin Sleep Cohort – a community-based sample – which found a positive relationship between OSA and increased mortality from cancer [20]. Nevertheless, to the best of our knowledge, the association between OSA and cancer mortality in a large clinical cohort has so far not been analyzed. Given the potential clinical impact of such an association – both in terms of prognosis and therapy – the aim of our study was to analyze the relationship between cancer mortality and the severity of OSA in a large sample of patients suspected of suffering from this sleep-disordered breathing.
Section snippets
Design and participants
This was a multicenter, longitudinal, retrospective cohort study in consecutive patients aged >18 years included in the databases of seven Spanish Sleep Units who had been assessed for suspected OSA between 2000 and 2007. We excluded patients with chronic respiratory failure (defined as chronic oxygen saturation <90% while breathing room air or prescribed domiciliary oxygen) or lack of available data on cancer, vital status or sleep study. The ethics committee of each center approved the study.
Data collection
Results
The initial analysis cohort included 5578 patients with clinical suspicion of OSA (Fig. 1). After applying the exclusion criteria, 5427 (97.5%) were included for analyses. Median age was 53.9 (13.1) years, and 22.2% were aged >65 years. Median (interquartile range [IQR]) AHI was 30 (14–52). CPAP was prescribed in 40.7% of patients. Data on TSat90 were available in 5131 patients (94.5%); 65.9% of patients underwent RP and 34.1% full PSG.
Table 1 shows the main baseline characteristics between
Discussion
To our knowledge this is the first study in the literature to analyze the association between OSA and cancer mortality in a large clinical cohort. We have found that OSA severity measured by overnight hypoxia was associated with increased cancer mortality. The closest association was seen, however, in patients aged <65 years. These results were replicated in the group of patients with a diagnosis of cancer.
Intermittent hypoxia is one of the most specific landmarks of OSA and plays an important
Funding source
(058/2011) Spanish Respiratory Society (SEPAR).
Conflict of interest
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2014.01.020.
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