Telomere Length and Risk of Major Adverse Cardiac Events and Cancer in Obstructive Sleep Apnea Patients

Telomere length (TL) is associated with cardiovascular disease (CVD) and cancer. Obstructive sleep apnea (OSA) is also linked to higher risk of CVD and cancer, and to TL. We investigated the association between TL and risk of major adverse cardiac events (MACE) and cancer in OSA patients. We studied 210 individuals undergoing sleep-related studies between 2000 and 2007. Baseline characteristics and follow-up data (available in 164 subjects) were obtained from clinic records. Incidence rates were calculated for the entire group and by OSA status. Hazard ratios were calculated to estimate effects of OSA and TL on risk of MACE and cancer. In total, 32 individuals (20%) developed MACE and/or cancer during 12.7-year follow-up. The OSA group had a higher likelihood of cancer (16.0 vs. 4.9 events per 1000 person-years, P = 0.044) but no clear evidence of an elevated incidence of MACE (10.8 vs. 4.8 events per 1000 person-years, P = 0.293) compared to the non-OSA group. There was no association between TL and MACE- (HR = 1.01, 95% CI 0.78–1.28), or cancer-risk (HR = 1.18, 95% CI 0.96–1.43). Our study warrants further investigation of any modulating effect of OSA on TL and the risk of MACE and cancer.

[1]  Sofie Bekaert,et al.  Telomere attrition as ageing biomarker. , 2005, Anticancer research.

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

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

[4]  F. Barbé,et al.  Cancer and OSA: Current Evidence From Human Studies. , 2016, Chest.

[5]  Adelaide M. Arruda-Olson,et al.  Sleep Apnea and Cardiovascular Disease , 2003, Herz.

[6]  E. Epel,et al.  Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection , 2015, Science.

[7]  R. Farré,et al.  Sleep apnoea and cancer: current insights and future perspectives , 2012, European Respiratory Journal.

[8]  Kevin E. Kip,et al.  The problem with composite end points in cardiovascular studies: the story of major adverse cardiac events and percutaneous coronary intervention. , 2008, Journal of the American College of Cardiology.

[9]  Vicente Andrés,et al.  Telomere Biology and Cardiovascular Disease , 2006, Circulation research.

[10]  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.

[11]  Chao-Yung Wang,et al.  Telomeres and Telomerase in Cardiovascular Diseases , 2016, Genes.

[12]  C. Guilleminault,et al.  EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association. , 1992, Sleep.

[13]  Tom R. Gaunt,et al.  Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study , 2017 .

[14]  A. Aviv,et al.  Telomere Length and Risk of Cancer and Non-neoplastic Diseases: Is Survivin the Ariadne's Thread?-Reply. , 2017, JAMA oncology.

[15]  Lin Kah Wai Telomeres, telomerase, and tumorigenesis--a review. , 2004, MedGenMed : Medscape general medicine.

[16]  R. Farré,et al.  Obstructive sleep apnea and cancer: Epidemiologic links and theoretical biological constructs. , 2016, Sleep medicine reviews.

[17]  B. Aggarwal,et al.  Oxidative stress, inflammation, and cancer: how are they linked? , 2010, Free radical biology & medicine.

[18]  S. Bojesen,et al.  Telomere Shortening Unrelated to Smoking, Body Weight, Physical Activity, and Alcohol Intake: 4,576 General Population Individuals with Repeat Measurements 10 Years Apart , 2014, PLoS genetics.

[19]  M. F. Troncoso,et al.  Sleep disordered breathing and nocturnal hypoxemia are very prevalent in a lung cancer screening population and may condition lung cancer screening findings: results of the prospective Sleep Apnea In Lung Cancer Screening (SAILS) study. , 2019, Sleep medicine.

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

[21]  D. Gozal,et al.  Sleep apnea and subsequent cancer incidence , 2018, Cancer Causes & Control.

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

[23]  S. Tufik,et al.  The paradigm of obstructive sleep apnea in aging: interactions with telomere length. , 2018, Sleep medicine.

[24]  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.

[25]  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.

[26]  Kazuhiko Fukuda,et al.  Proposed supplements and amendments to ‘A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects’, the Rechtschaffen & Kales (1968) standard , 2001, Psychiatry and clinical neurosciences.

[27]  Wei Chen,et al.  Leukocyte Telomere Dynamics: Longitudinal Findings Among Young Adults in the Bogalusa Heart Study , 2008, American journal of epidemiology.

[28]  O. Alqawi,et al.  Chronic hypoxia promotes an aggressive phenotype in rat prostate cancer cells , 2007, Free radical research.

[29]  V. Somers,et al.  Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening. , 2017, American journal of physiology. Heart and circulatory physiology.

[30]  R. Cawthon Telomere measurement by quantitative PCR. , 2002, Nucleic acids research.

[31]  M. Shammas Telomeres, lifestyle, cancer, and aging , 2011, Current opinion in clinical nutrition and metabolic care.

[32]  M Ashcroft,et al.  Hypoxic regulation of telomerase gene expression by transcriptional and post-transcriptional mechanisms , 2006, Oncogene.

[33]  David N. Rider,et al.  Correlation of Chromosomal Instability, Telomere Length and Telomere Maintenance in Microsatellite Stable Rectal Cancer: A Molecular Subclass of Rectal Cancer , 2013, PloS one.

[34]  E. Wolpert A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. , 1969 .

[35]  Liza S. M. Wong,et al.  Telomere length loss due to smoking and metabolic traits , 2014, Journal of internal medicine.

[36]  M. F. Troncoso,et al.  Sleep Disordered Breathing Is Highly Prevalent in Patients with Lung Cancer: Results of the Sleep Apnea in Lung Cancer Study , 2018, Respiration.

[37]  Ahmedin Jemal,et al.  Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States , 2018, CA: a cancer journal for clinicians.

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

[39]  T. Maeda,et al.  Different levels of hypoxia regulate telomere length and telomerase activity , 2012, Aging Clinical and Experimental Research.

[40]  Jiping Li,et al.  The association between obstructive sleep apnea and shortened telomere length: a systematic review and meta-analysis. , 2017, Sleep medicine.

[41]  N. Sarrafzadegan,et al.  Cardiovascular disease and cancer: Evidence for shared disease pathways and pharmacologic prevention. , 2017, Atherosclerosis.

[42]  A. Möller,et al.  Intermittent hypoxia induces a metastatic phenotype in breast cancer , 2018, Oncogene.

[43]  L. Kheirandish-Gozal,et al.  Leukocyte telomere length and plasma catestatin and myeloid-related protein 8/14 concentrations in children with obstructive sleep apnea. , 2010, Chest.

[44]  M. Haussmann,et al.  Telomere dynamics may link stress exposure and ageing across generations , 2015, Biology Letters.

[45]  H. Gerstein,et al.  Association Between Shortened Leukocyte Telomere Length and Cardiometabolic Outcomes: Systematic Review and Meta-Analysis , 2015, Circulation. Cardiovascular genetics.

[46]  A. Aviv,et al.  Mutations, Cancer and the Telomere Length Paradox. , 2017, Trends in cancer.

[47]  Yuling Hong,et al.  Heart Disease and Cancer Deaths — Trends and Projections in the United States, 1969–2020 , 2016, Preventing chronic disease.

[48]  A. Blaes,et al.  Shared Risk Factors in Cardiovascular Disease and Cancer , 2016, Circulation.

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

[50]  A. Lowe,et al.  Prevalence of obstructive sleep apnea in the general population: A systematic review. , 2017, Sleep medicine reviews.

[51]  Kristina M. Cook,et al.  Models of intermittent hypoxia and obstructive sleep apnea: molecular pathways and their contribution to cancer. , 2018, American journal of physiology. Regulatory, integrative and comparative physiology.

[52]  T. Young,et al.  Sleep apnea and cardiovascular disease: an American Heart Association/American College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Coun , 2008, Journal of the American College of Cardiology.

[53]  Stephen Kaptoge,et al.  Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis , 2014, BMJ : British Medical Journal.

[54]  G. Jin,et al.  The association between telomere length and cancer risk in population studies , 2016, Scientific Reports.

[55]  D. Navajas,et al.  Intermittent hypoxia enhances cancer progression in a mouse model of sleep apnoea , 2011, European Respiratory Journal.

[56]  Pim van der Harst,et al.  Telomere biology in healthy aging and disease , 2009, Pflügers Archiv - European Journal of Physiology.