Original ArticleSleep apnea increased incidence of primary central nervous system cancers: a nationwide cohort study
Introduction
Patients with obstructive sleep apnea (OSA) and poor quality of sleep may be at increased risk for obesity, diabetes mellitus (DM), cardiovascular disease, cognitive impairment and total mortality [1], [2]. OSA also may contribute to several organ system dysfunctions including auditory [3] and ophthalmic [4] degeneration, as well as overactive bladder [5]. However, little information is available regarding the association of OSA and tumor formation. Evidence shows that tumor hypoxia and its related molecular mediators regulate multiple steps of tumorigenesis, including tumor formation, progression, and response to therapy [6]. Hypoxia also plays a role in glioma tumorigenesis [7]. The progression of low-grade astrocytoma to glioblastoma multiforme may be mediated by hypoxia-induced phenotypic changes and subsequent clonal selection of cells that overexpress hypoxia-responsive molecules [7], [8]. From these experimental observations, we hypothesized that OSA and subsequent tissue hypoxia might lead to cancer formation. However, this relationship in humans has not yet been firmly established.
A previous study showed that short duration of sleep increased the risk for colorectal adenoma [9]. It has been reported that an adequate night of sleep may reduce the risk for breast cancer [10], [11]. Recently, OSA was associated with increased incidence of all cancers, especially in men and patients younger than the age of 65 years in a large multicenter Spanish cohort study [12]. Thus it seems that sleep apnea may increase the risk for malignant tumors at various sites. Because the central nervous system (CNS) is a high oxygen-demanding organ, it may be prone to hypoxia damage. Moreover, tissue hypoxia resulting from sleep apnea may increase the risk for cancer formation, but it remains unclear if OSA can increase the risk for primary CNS cancers in humans. Therefore, our study aimed to address this concern.
Section snippets
Study design and data collection
Our study used data retrieved from the medical claims database of Taiwan’s National Health Institute (NHI) program. In Taiwan, National Health Care is obligatory and individuals rarely are excluded from this system. Thus the NHI program covers more than 96% of the population in the country and has contracted with 97% of all hospitals and clinics in Taiwan [13]. The study protocol was approved by the Institutional Review Board of Dalin Tzu Chi Hospital. Further, this board waived the need for
Participant characteristics
Table 1 shows the clinical characteristics of both study cohorts. All comorbidities, including obesity, CAD, HTN, DM, dyslipidemia, CKD, chronic hepatitis, liver cirrhosis, CVD, PD and AD were more prevalent in the OSA group than in the comparison group.
Incidence of primary CNS cancers
During the 10-year follow-up period, we identified 38 cases (0.16%) of primary CNS cancer (brain [n = 32] and spinal cord [n = 6]) in the OSA group and 85 cases (0.12%) of CNS cancer (brain [n = 65] and spinal cord [n = 20]) in the comparison group (
Discussion
Our cohort study observed the medical claims database of Taiwan’s NHI program as the data source, and showed that OSA may increase the risk or precede the development of primary CNS cancers. Nevertheless, surgical treatment may reduce the risk for primary CNS cancers. This clinical observation supports experimental findings showing that hypoxia can lead to tumor formation including formation of primary CNS tumors [6], [7], [8], [14].
To our knowledge only a limited number of risk factors have
Conclusion
The results of our retrospective cohort study suggest that OSA can precede or increase the risk for primary malignant CNS cancer development. Moreover, surgical treatment may reduce the risk for primary CNS cancers in patients with OSA. We suggest that OSA should be more aggressively treated and clinicians should pay more attention to the OSA-related sequelae.
Funding sources
Our study was supported by grants (DTCRD100-2-I-03) from the Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
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.2013.11.782.
Acknowledgment
We thank Assistant Professor Tzung-Yi Tsai and Associate Professor Malcolm Koo in Dalin Tzu Chi Hospital for providing statistical consultation in our study.
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