SLEEP-DISORDERED BREATHING Sleep Apnea and Cancer : Analysis of a Nationwide Population Sample

STUDY OBJECTIVES Epidemiological evidence from relatively small cohorts suggests that obstructive sleep apnea (OSA) is associated with higher cancer incidence and mortality. Here we aimed to determine whether cancer incidence for major cancer types and risk of metastases or mortality from cancer are increased in the presence of OSA. METHODS All OSA diagnoses included in an employee-sponsored health insurance database spanning the years 2003-2012 were identified and 1:1 matched demographically based on age, gender, and state of residence, or alternatively matched by comorbidities. The incidence of 12 types of cancer was assessed. In addition, another cohort of patients with a primary diagnosis of cancer was retrieved, and the risk of metastatic disease or cancer mortality was determined as a function of the presence or absence of OSA. Multivariate Cox proportional hazards regression models were fitted to assess the independent associations between OSA and outcomes of interest. RESULTS Based on a cohort of ∼5.6 million individuals, the incidence of all cancer diagnoses combined was similar in OSA and retrospectively matched cases. However, the adjusted risk of pancreatic and kidney cancer and melanoma were significantly higher in patients with OSA, while the risk of colorectal, breast, and prostate cancers appeared to be lower. Among individuals with a diagnosis of cancer, the presence of OSA was not associated with an increased risk for metastasis or death. CONCLUSIONS In a large nationally representative health insurance database, OSA appears to increase the risk for only a very selective number of cancer types, and does not appear to be associated with an increased risk of metastatic cancer or cancer-related deaths.

[1]  Sanjay R. Patel,et al.  Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes. , 2014, Sleep.

[2]  R. Montironi,et al.  Survival in patients with clear cell renal cell carcinoma is predicted by HIF-1α expression. , 2015, Anticancer research.

[3]  A. White,et al.  Targeting hypoxia in the treatment of small cell lung cancer. , 2014, Lung cancer.

[4]  R. Farré,et al.  Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. , 2014, American journal of respiratory and critical care medicine.

[5]  T. Sooronbaev,et al.  Prevalence of obstructive sleep apnea in Asian adults: a systematic review of the literature , 2013, BMC Pulmonary Medicine.

[6]  Takuji Tanaka,et al.  Chemoprevention of colorectal cancer by targeting obesity-related metabolic abnormalities. , 2014, World journal of gastroenterology.

[7]  Terry Young,et al.  Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study. , 2012, American journal of respiratory and critical care medicine.

[8]  W. Trzepizur,et al.  [Epidemiology of obstructive sleep apnoea syndrome]. , 2014, Revue des maladies respiratoires.

[9]  Pierre Philip,et al.  Impact of sleep apnea on economics. , 2012, Sleep medicine reviews.

[10]  W. Trzepizur,et al.  [Epidemiology of obstructive sleep apnoea syndrome]. , 2014, Revue des maladies respiratoires.

[11]  M. Preisig,et al.  Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. , 2015, The Lancet. Respiratory medicine.

[12]  M. Villalona-Calero,et al.  Race and Ethnicity in Cancer Therapy: What Have We Learned? , 2014, Clinical pharmacology and therapeutics.

[13]  M. Grigg‐Damberger,et al.  Roles of gender, age, race/ethnicity, and residential socioeconomics in obstructive sleep apnea syndromes , 2012, Current opinion in pulmonary medicine.

[14]  Mary J Morrell,et al.  Sleep apnoea and the brain: a complex relationship. , 2015, The Lancet. Respiratory medicine.

[15]  Carolien P. Schröder,et al.  BMI and Lifetime Changes in BMI and Cancer Mortality Risk , 2015, PloS one.

[16]  L. Cheskin,et al.  Association between sleep-disordered breathing, obstructive sleep apnea, and cancer incidence: a systematic review and meta-analysis. , 2015, Sleep medicine.

[17]  Ronald R Grunstein,et al.  Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton Health Study cohort. , 2014, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[18]  D. Navajas,et al.  Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea , 2013, Respiratory Physiology & Neurobiology.

[19]  C. Moretti,et al.  Association of epicardial fat thickness with the severity of obstructive sleep apnea in obese patients. , 2013, International journal of cardiology.

[20]  D. Clegg,et al.  Obesity and cancer—mechanisms underlying tumour progression and recurrence , 2014, Nature Reviews Endocrinology.

[21]  Zhen-ning Wang,et al.  Influence of different hypoxia models on metastatic potential of SGC-7901 gastric cancer cells , 2014, Tumor Biology.

[22]  G. Tomlinson,et al.  Obstructive sleep apnea and the prevalence and incidence of cancer , 2014, Canadian Medical Association Journal.

[23]  R. Farré,et al.  Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort. , 2013, American journal of respiratory and critical care medicine.

[24]  H. Nakano,et al.  Cross-cultural comparison of the sleep-disordered breathing prevalence among Americans and Japanese , 2010, European Respiratory Journal.

[25]  N. H. Rod,et al.  Symptoms of sleep disordered breathing and risk of cancer: a prospective cohort study. , 2013, Sleep.

[26]  C. Cerdá,et al.  Oxidative stress and DNA damage in obesity-related tumorigenesis. , 2014, Advances in experimental medicine and biology.

[27]  M. Jarzab,et al.  Global Gene Expression Profiling in Three Tumor Cell Lines Subjected to Experimental Cycling and Chronic Hypoxia , 2014, PloS one.

[28]  D. Gozal,et al.  Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. , 2014, Cancer research.

[29]  A. Weeraratna,et al.  Change is in the air: the hypoxic induction of phenotype switching in melanoma. , 2013, The Journal of investigative dermatology.

[30]  Juen-Haur Hwang,et al.  Sleep apnea increased incidence of primary central nervous system cancers: a nationwide cohort study. , 2014, Sleep medicine.

[31]  H. Reuveni,et al.  The economic impact of obstructive sleep apnea , 2013, Current opinion in pulmonary medicine.

[32]  A. Renehan,et al.  Excess adiposity and gastrointestinal cancer , 2014, The British journal of surgery.

[33]  C. van Walraven,et al.  Identifying Obstructive Sleep Apnea in Administrative Data: A Study of Diagnostic Accuracy , 2015, Anesthesiology.

[34]  A. Yang,et al.  Sleep apnea and the subsequent risk of breast cancer in women: a nationwide population-based cohort study. , 2014, Sleep medicine.

[35]  V. Polotsky,et al.  Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. , 2013, Journal of the American College of Cardiology.

[36]  J. Robbins,et al.  Sleep disturbances, quality of life, and ethnicity: the Sleep Heart Health Study. , 2010, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[37]  J. Handa,et al.  Hypoxia Promotes Uveal Melanoma Invasion through Enhanced Notch and MAPK Activation , 2014, PloS one.

[38]  L. Lavie,et al.  Oxidative stress--a unifying paradigm in obstructive sleep apnea and comorbidities. , 2009, Progress in cardiovascular diseases.

[39]  J. Mak,et al.  Obesity, obstructive sleep apnoea and metabolic syndrome , 2012, Respirology.

[40]  R. Farré,et al.  Association between sleep disordered breathing and aggressiveness markers of malignant cutaneous melanoma , 2014, European Respiratory Journal.

[41]  R. Moon,et al.  Assessment of Hypoxia Inducible Factor Levels in Cancer Cell Lines upon Hypoxic Induction Using a Novel Reporter Construct , 2011, PloS one.

[42]  C. Chai-Coetzer,et al.  Obstructive sleep apnoea in adults: a common chronic condition in need of a comprehensive chronic condition management approach. , 2013, Sleep medicine reviews.

[43]  H. Moch,et al.  A clearer view of the molecular complexity of clear cell renal cell carcinoma. , 2015, Annual review of pathology.

[44]  A. Jemal,et al.  Prevalence of Major Risk Factors and Use of Screening Tests for Cancer in the United States , 2015, Cancer Epidemiology, Biomarkers & Prevention.

[45]  H. Colman,et al.  Intermittent Induction of HIF-1α Produces Lasting Effects on Malignant Progression Independent of Its Continued Expression , 2015, PloS one.

[46]  R. Farré,et al.  Obstructive sleep apnea is associated with cancer mortality in younger patients. , 2014, Sleep medicine.

[47]  Kehu Yang,et al.  The expression of hypoxia-inducible factor-1α and its clinical significance in lung cancer: a systematic review and meta-analysis. , 2013, Swiss medical weekly.