Advertisement

Association Between Nocturnal Hypoxemia and Cancer Incidence in Patients Investigated for OSA

Data From a Large Multicenter French Cohort

      Background

      Previous studies have yielded inconsistent findings regarding the association between OSA and cancer in humans.

      Research Question

      Is there an association between indexes of sleep-disordered breathing severity and cancer incidence in patients investigated for suspected OSA?

      Study Design and Methods

      Data from a large multicenter cohort of cancer-free patients investigated for OSA were linked to health administrative data to identify new-onset cancer. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association of cancer incidence with OSA severity and nocturnal hypoxemia.

      Results

      After a median follow-up period of 5.8 years (interquartile range, 3.8-7.8), 718 of 8,748 patients (8.2%) had received a diagnosis of cancer. On unadjusted Kaplan-Meier survival analyses, cancer incidence was associated with increasing severity of OSA (log-rank test, P < .0005) and nocturnal hypoxemia (log-rank test, P < .0001 for both oxygen desaturation index and percent night time with oxygen saturation < 90% [T90]). After adjustment for anthropomorphic data, smoking and alcohol consumption, comorbid cardiac, metabolic, and respiratory diseases, marital status, type of sleep study, and study site, only T90 was associated with cancer incidence (adjusted hazard ratio, 1.33; 95% CI, 1.05-1.68 for T90 ≥ 13% vs < 0.01%; P = .02). On stratified analyses, the association between T90 and cancer appeared stronger in older patients with obesity and no adequate OSA therapy. Among the most frequent cancer sites, nocturnal hypoxemia was associated with lung and breast malignancies.

      Interpretation

      Nocturnal hypoxemia was associated with all-cancer incidence in patients investigated for OSA. Whether OSA therapy might reduce the risk of cancer needs further evaluation.

      Key Words

      Abbreviations:

      AHI (apnea-hypopnea index), HR (hazard ratio), IH (intermittent hypoxemia), IQR (interquartile range), ODI (oxygen desaturation index), PAP (positive airway pressure), PMSI (Programme de Medicalisation des Systemes d’Information), PSG (polysomnography), SNDS (French administrative health-care database), T90 (percent night time with oxygen saturation < 90%)
      To read this article in full you will need to make a payment
      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Gozal D.
        • Farré R.
        • Nieto F.J.
        Obstructive sleep apnea and cancer: epidemiologic links and theoretical biological constructs.
        Sleep Med Rev. 2016; 27: 43-55
        • Nieto F.J.
        • Peppard P.E.
        • Young T.
        • Finn L.
        • Hla K.M.
        • Farré R.
        Sleep-disordered breathing and cancer mortality.
        Am J Respir Crit Care Med. 2012; 186: 190-194
        • Marshall N.S.
        • Wong K.K.H.
        • Cullen S.R.J.
        • Knuiman M.W.
        • Grunstein R.R.
        Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton health study cohort.
        J Clin Sleep Med. 2014; 10: 355-362
        • Christensen A.S.
        • Clark A.
        • Salo P.
        • et al.
        Symptoms of sleep disordered breathing and risk of cancer: a prospective cohort study.
        Sleep. 2013; 36: 1429-1435
        • Fang H.-F.
        • Miao N.-F.
        • Chen C.-D.
        • Sithole T.
        • Chung M.-H.
        Risk of cancer in patients with insomnia, parasomnia, and obstructive sleep apnea: a nationwide nested case-control study.
        J Cancer. 2015; 6: 1140-1147
        • Gozal D.
        • Ham S.A.
        • Mokhlesi B.
        Sleep apnea and cancer: analysis of a nationwide population sample.
        Sleep. 2016; 39: 1493-1500
        • Campos-Rodriguez F.
        • Martinez-Garcia M.A.
        • Martinez M.
        • et al.
        Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort.
        Am J Respir Crit Care Med. 2013; 187: 99-105
        • Brenner R.
        • Kivity S.
        • Peker M.
        • et al.
        Increased risk for cancer in young patients with severe obstructive sleep apnea.
        Respir Int Rev Thorac Dis. 2019; 97: 15-23
        • Sillah A.
        • Watson N.F.
        • Gozal D.
        • Phipps A.I.
        Obstructive sleep apnea severity and subsequent risk for cancer incidence.
        Prev Med Rep. 2019; 15: 100886
        • Kendzerska T.
        • Leung R.S.
        • Hawker G.
        • Tomlinson G.
        • Gershon A.S.
        Obstructive sleep apnea and the prevalence and incidence of cancer.
        CMAJ. 2014; 186: 985-992
        • Gagnadoux F.
        • Le Vaillant M.
        • Goupil F.
        • et al.
        Influence of marital status and employment status on long-term adherence with continuous positive airway pressure in sleep apnea patients.
        PLoS One. 2011; 6e22503
        • Fagot J.-P.
        • Blotière P.-O.
        • Ricordeau P.
        • Weill A.
        • Alla F.
        • Allemand H.
        Does insulin glargine increase the risk of cancer compared with other basal insulins?: a French nationwide cohort study based on national administrative databases.
        Diabetes Care. 2013; 36: 294-301
        • Gagnadoux F.
        • Le Vaillant M.
        • Goupil F.
        • et al.
        Depressive symptoms before and after long-term CPAP therapy in patients with sleep apnea.
        Chest. 2014; 145: 1025-1031
        • Meurice J.-C.
        • Gagnadoux F.
        Recommendations for clinical practice in the management of obstructive sleep apnea syndrome in adults. Preface [in French].
        Rev Mal Respir. 2010; 27: S113-S114
        • Berry R.B.
        • Budhiraja R.
        • Gottlieb D.J.
        • et al.
        Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine.
        J Clin Sleep Med. 2012; 8: 597-619
        • National Cancer Institute
        Algorithm for selecting hospitalizations linked to cancer in OCD - Validation study.
        • Remontet L.
        • Mitton N.
        • Couris C.M.
        • et al.
        Is it possible to estimate the incidence of breast cancer from medico-administrative databases?.
        Eur J Epidemiol. 2008; 23: 681-688
        • Mitton N.
        • Colonna M.
        • Trombert B.
        • et al.
        A suitable approach to estimate cancer incidence in area without cancer registry.
        J Cancer Epidemiol. 2011; 2011: 1-11
        • Quantin C.
        • Benzenine E.
        • Hägi M.
        • et al.
        Estimation of national colorectal-cancer incidence using claims databases.
        J Cancer Epidemiol. 2012; 2012: 1-7
        • Azarbarzin A.
        • Sands S.A.
        • Stone K.L.
        • et al.
        The hypoxic burden of sleep apnoea predicts cardiovascular disease-related mortality: the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study.
        Eur Heart J. 2019; 40: 1149-1157
        • Kendzerska T.
        • Gershon A.S.
        • Atzema C.
        • et al.
        Sleep apnea increases the risk of new hospitalized atrial fibrillation: a historical cohort study.
        Chest. 2018; 154: 1330-1339
        • Li J.
        • Savransky V.
        • Nanayakkara A.
        • Smith P.L.
        • O’Donnell C.P.
        • Polotsky V.Y.
        Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia.
        J Appl Physiol Bethesda Md 1985. 2007; 102: 557-563
        • Kendzerska T.
        • Gershon A.S.
        • Hawker G.
        • Leung R.S.
        • Tomlinson G.
        Obstructive sleep apnea and risk of cardiovascular events and all-cause mortality: a decade-long historical cohort study.
        PLoS Med. 2014; 11e1001599
        • Simpson S.H.
        • Eurich D.T.
        • Majumdar S.R.
        • et al.
        A meta-analysis of the association between adherence to drug therapy and mortality.
        BMJ. 2006; 333: 15
        • Vestbo J.
        • Anderson J.A.
        • Calverley P.M.A.
        • et al.
        Adherence to inhaled therapy, mortality and hospital admission in COPD.
        Thorax. 2009; 64: 939-943
        • Kendzerska T.
        • Leung R.S.
        • Gershon A.S.
        • Tomlinson G.
        • Ayas N.
        The interaction of obesity and nocturnal hypoxemia on cardiovascular consequences in adults with suspected obstructive sleep apnea. a historical observational study.
        Ann Am Thorac Soc. 2016; 13: 2234-2241
        • Peppard P.E.
        • Ward N.R.
        • Morrell M.J.
        The impact of obesity on oxygen desaturation during sleep-disordered breathing.
        Am J Respir Crit Care Med. 2009; 180: 788-793
        • Seijo L.M.
        • Pérez-Warnisher M.T.
        • Giraldo-Cadavid L.F.
        • et al.
        Obstructive sleep apnea and nocturnal hypoxemia are associated with an increased risk of lung cancer.
        Sleep Med. 2019; 63: 41-45
        • Chang W.-P.
        • Liu M.-E.
        • Chang W.-C.
        • et al.
        Sleep apnea and the subsequent risk of breast cancer in women: a nationwide population-based cohort study.
        Sleep Med. 2014; 15: 1016-1020
        • Li L.
        • Lu J.
        • Xue W.
        • et al.
        Target of obstructive sleep apnea syndrome merge lung cancer: based on big data platform.
        Oncotarget. 2017; 8: 21567-21578
        • Bezin J.
        • Duong M.
        • Lassalle R.
        • et al.
        The national healthcare system claims databases in France, SNIIRAM and EGB: powerful tools for pharmacoepidemiology.
        Pharmacoepidemiol Drug Saf. 2017; 26: 954-962
        • Tuppin P.
        • Rudant J.
        • Constantinou P.
        • et al.
        Value of a national administrative database to guide public decisions: from the système national d’information interrégimes de l’Assurance Maladie (SNIIRAM) to the système national des données de santé (SNDS) in France.
        Rev Epidemiol Sante Publique. 2017; 65: S149-S167
        • Scailteux L.-M.
        • Droitcourt C.
        • Balusson F.
        • et al.
        French administrative health care database (SNDS): the value of its enrichment.
        Therapie. 2019; 74: 215-223
        • Grigg-Damberger M.M.
        The AASM Scoring Manual four years later.
        J Clin Sleep Med. 2012; 8: 323-332