Elsevier

Sleep Medicine

Volume 15, Issue 7, July 2014, Pages 742-748
Sleep Medicine

Original Article
Obstructive sleep apnea is associated with cancer mortality in younger patients

https://doi.org/10.1016/j.sleep.2014.01.020Get rights and content

Abstract

Objective

The association between obstructive sleep apnea (OSA) and cancer mortality has scarcely been studied. The objective of this study was to investigate whether OSA is associated with increased cancer mortality in a large cohort of patients with OSA suspicion.

Methods

This was a multicenter study in consecutive patients investigated for suspected OSA. OSA severity was measured by the apnea–hypopnea index (AHI) and the hypoxemia index (% night-time spent with oxygen saturation <90%, TSat90). The association between OSA severity and cancer mortality was assessed using Cox’s proportional regression analyses after adjusting for relevant confounders.

Results

In all, 5427 patients with median follow-up of 4.5 years were included. Of these, 527 (9.7%) were diagnosed with cancer. Log-transformed TSat90 was independently associated with increased cancer mortality in the entire cohort (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03–1.42), as well as in the group of patients with cancer (HR, 1.19; 95% CI, 1.02–1.41). The closest association was shown in patients <65 years in both the AHI (continuous log-transformed AHI: HR, 1.87; 95% CI, 1.1–3.2; upper vs lower AHI tertile: HR, 3.98; 95% CI, 1.14–3.64) and the TSat90 (continuous log-transformed TSat90: HR, 1.73; 95% CI, 1.23–2.4; upper vs lower TSat90 tertile: HR, 14.4; 95% CI, 1.85–111.6).

Conclusions

OSA severity was associated with increased cancer mortality, particularly in patients aged <65 years.

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.

. ICMJE Form for Disclosure of Potential Conflicts of Interest form.

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