Top

Cancer Causes & Control

Published in:

01-10-2018 | Original paper

Sleep apnea and subsequent cancer incidence

Authors: Arthur Sillah, Nathaniel F. Watson, Stephen M. Schwartz, David Gozal, Amanda I. Phipps

Published in: Cancer Causes & Control | Issue 10/2018

Abstract

Purpose

In vitro and animal models suggest that the physiological effects of sleep apnea could contribute to cancer risk, yet epidemiologic studies have been inconsistent.

Methods

We identified a cohort of adults diagnosed with sleep apnea between 2005 and 2014 using regional administrative databases. Linking this cohort to a population-based cancer registry, we identified first incident cancers diagnosed after sleep apnea diagnosis through 2015. We calculated age–sex standardized cancer incidence ratios (SIRs) to compare the observed number of cancers among those with sleep apnea with expected population estimates over a comparable period.

Results

Among 34,402 individuals with sleep apnea, 1,575 first incident cancers were diagnosed during follow-up (mean ± SD; 5.3 ± 2.0 years). Compared to the general population, cancer incidence (SIR 1.26, 95% CI 1.20–1.32) was elevated among sleep apnea patients. We observed significantly elevated incidence for kidney (SIR 2.24, 95% CI 1.82–2.72), melanoma (SIR 1.71, 95% CI 1.42–2.03), breast (SIR 1.43, 95% CI 1.76–2.00), and corpus uteri (SIR 2.80, 95% CI 2.24–2.47) while risk for lung (SIR 0.66, 95% CI 0.54–0.79) and colorectal cancer (SIR 0.71, 95% CI 0.56–0.89) was lower.

Conclusion

These findings suggest an elevated cancer burden, particularly at certain sites, among individuals with diagnosed sleep apnea. Results should be interpreted with caution due to unmeasured confounders (e.g., BMI, diabetes).

Available only for authorised users

Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM (2013) Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177(9):1006–1014. https://doi.org/10.1093/aje/kws342 CrossRefPubMedCentralPubMed

Acker J, Richter K, Piehl A, Herold J, Ficker J, Niklewski G. Obstructive sleep apnea (OSA) and clinical depression—prevalence in a sleep center. Sleep and Breathing. 2016:1–8

Barger LK, Rajaratnam S, Wang W, OBrien CS, Sullivan JP, Quadri S (2015) Common sleep disorders increase risk of motor vehicle crashes and adverse health outcomes in firefighters. J Clin Sleep Med 11(3):233–240PubMedCentralPubMed

Clark AJ, Salo P, Lange T et al. Onset of impaired sleep and cardiovascular disease risk factors: A longitudinal study.. 2016

Covassin N, Somers VK (2016) Sleep apnea, hypertension, and hemorrhagic stroke—déjà vu all over again. Journal of the American Society of Hypertension 10(3):197–200CrossRefPubMed

Kendzerska T, Gershon AS, Hawker G, Tomlinson G, Leung RS (2014) Obstructive sleep apnea and incident diabetes. A historical cohort study. American journal of respiratory critical care medicine 190(2):218–225CrossRefPubMed

Tarasiuk A, Reuveni H (2013) The economic impact of obstructive sleep apnea. Curr Opin Pulm Med 19(6):639–644. https://doi.org/10.1097/MCP.0b013e3283659e1e CrossRefPubMed

Kao L, Lee H, Lin H, Tsai M, Chung S (2015) Healthcare service utilization by patients with obstructive sleep apnea: A population-based study. PloS one 10(9):e0137459CrossRefPubMedPubMedCentral

Li L, Ren F, Cao J, Chen B (2016) Relevant mechanism of intermittent hypoxia-induced melanoma lung metastases in a murine model of sleep apnea. CHEST Journal 149(4_S):A556–A556CrossRef

10.

Khalyfa A, Almendros I, Gileles-Hillel A et al (2016) Circulating exosomes potentiate tumor malignant properties in a mouse model of chronic sleep fragmentation. Oncotarget. https://doi.org/10.18632/oncotarget.10578

11.

Zheng J, Almendros I, Wang Y et al (2015) Reduced NADPH oxidase type 2 activity mediates sleep fragmentation-induced effects on TC1 tumors in mice. OncoImmunology 4(2):e976057CrossRefPubMedPubMedCentral

12.

Gozal D, Farré R, Nieto FJ (2015) Putative links between sleep apnea and cancer: From hypotheses to evolving evidence. CHEST Journal 148(5):1140–1147CrossRef

13.

Hakim F, Wang Y, Zhang SX et al (2014) Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res 74(5):1329–1337. https://doi.org/10.1158/0008-5472.CAN-13-3014 CrossRefPubMedCentralPubMed

14.

Nanduri J, Prabhakar NR. Intermittent hypoxia: Mechanistic pathways influencing cancer. In: Impact of sleep and sleep disturbances on obesity and cancer. Springer; 2014:103–119

15.

Miao Z, Zhao T, Wang Z et al (2014) Influence of different hypoxia models on metastatic potential of SGC-7901 gastric cancer cells. Tumor Biol 35(7):6801–6808CrossRef

16.

Zhang J, Guo X, Shi Y, Ma J, Wang G (2014) Intermittent hypoxia with or without hypercapnia is associated with tumorigenesis by decreasing the expression of brain derived neurotrophic factor and miR-34a in rats. Chin Med J (Engl) 127(1):43–47

17.

Almendros I, Montserrat JM, Torres M et al (2013) Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea. Respiratory physiology neurobiology 186(3):303–307CrossRefPubMed

18.

Almendros I, Montserrat JM, Ramirez J et al (2012) Intermittent hypoxia enhances cancer progression in a mouse model of sleep apnoea. Eur Respir J 39(1):215–217. https://doi.org/10.1183/09031936.00185110 CrossRefPubMed

19.

Wan J, Chai H, Yu Z et al (2011) HIF-1α effects on angiogenic potential in human small cell lung carcinoma. Journal of Experimental Clinical Cancer Research 30(1):1CrossRef

20.

Liu Y, Song X, Wang X et al (2010) Effect of chronic intermittent hypoxia on biological behavior and hypoxia-associated gene expression in lung cancer cells. J Cell Biochem 111(3):554–563CrossRefPubMed

21.

Rofstad EK, Gaustad J, Egeland TA, Mathiesen B, Galappathi K (2010) Tumors exposed to acute cyclic hypoxic stress show enhanced angiogenesis, perfusion and metastatic dissemination. International journal of cancer 127(7):1535–1546CrossRefPubMed

22.

Toffoli S, Michiels C (2008) Intermittent hypoxia is a key regulator of cancer cell and endothelial cell interplay in tumours. FEBS journal 275(12):2991–3002CrossRefPubMed

23.

Carmeliet P, Dor Y, Herbert J et al (1998) Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394(6692):485–490CrossRefPubMed

24.

Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359(6398):843–845. https://doi.org/10.1038/359843a0 CrossRefPubMed

25.

Fang H, Miao N, Chen C, Sithole T, Chung M (2015) Risk of cancer in patients with insomnia, parasomnia, and obstructive sleep apnea: A nationwide nested case-control study. Journal of Cancer 6(11):1140CrossRefPubMedPubMedCentral

26.

Marshall NS, Wong K, Cullen S, Knuiman MW, Grunstein RR (2014) 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 10(4):355–362PubMedCentralPubMed

27.

Campos-Rodriguez F, Martinez-Garcia MA, Martinez M et al (2013) Association between obstructive sleep apnea and cancer incidence in a large multicenter spanish cohort. American journal of respiratory critical care medicine 187(1):99–105CrossRefPubMed

28.

Christensen AS, Clark A, Salo P et al (2013) Symptoms of sleep disordered breathing and risk of cancer: A prospective cohort study. Sleep 36(10):1429–1435. https://doi.org/10.5665/sleep.3030 CrossRefPubMedCentralPubMed

29.

Gozal D, Ham SA, Mokhlesi B (2016) Sleep apnea and cancer: Analysis of a nationwide population sample. Sleep 39(8):1493–1500. https://doi.org/10.5665/sleep.6004 CrossRefPubMedCentralPubMed

30.

Kendzerska T, Leung RS, Hawker G, Tomlinson G, Gershon AS (2014) Obstructive sleep apnea and the prevalence and incidence of cancer. CMAJ 186(13):985–992. https://doi.org/10.1503/cmaj.140238 CrossRefPubMedCentralPubMed

31.

Nieto FJ, Peppard PE, Young T, Finn L, Hla KM, Farré R (2012) Sleep-disordered breathing and cancer mortality: Results from the wisconsin sleep cohort study. American journal of respiratory critical care medicine 186(2):190–194CrossRefPubMedPubMedCentral

32.

Martinez-Garcia MA, Campos-Rodriguez F, Duran-Cantolla J et al (2014) Obstructive sleep apnea is associated with cancer mortality in younger patients. Sleep Med 15(7):742–748. https://doi.org/10.1016/j.sleep.2014.01.020 CrossRefPubMed

33.

Chang W, Liu M, Chang W et al (2014) Sleep apnea and the subsequent risk of breast cancer in women: a nationwide population-based cohort study. Sleep Med 15(9):1016–1020CrossRefPubMed

34.

Chen J, Hwang J (2014) Sleep apnea increased incidence of primary central nervous system cancers: A nationwide cohort study. Sleep Med 15(7):749–754CrossRefPubMed

35.

Foldvary-Schaefer NR, Waters TE (2017) Sleep-disordered breathing. Continuum (Minneap Minn) 23(4):Sleep Neurology):1093–1116. https://doi.org/10.1212/01.CON.0000522245.13784.f6 CrossRef

36.

Surveillance, epidemiology, and end results program (SEER) seattle-puget sound registry. https://Seer.cancer.gov/registries/sps.html. Accessed 23 May 2017

37.

Fritz AG, RHIT C, Hurlbut AA et al (2001) SEER summary staging manual-2000: codes and coding instructions. National Cancer Institute, Bethesda

38.

Surveillance research program, national cancer institute SEER*Stat software (http://www.seer.cancer.gov/seerstat) version 8.3.4.

39.

StataCorp (2015) Stata statistical software: release 14. StataCorp LP, College station

40.

Almendros I, Gileles-Hillel A, Khalyfa A et al (2015) Adipose tissue macrophage polarization by intermittent hypoxia in a mouse model of OSA: effect of tumor microenvironment. Cancer Lett 361(2):233–239CrossRefPubMed

41.

Akbarpour M, Khalyfa A, Qiao Z et al (2016) Altered CD8+ T-cell lymphocyte function and TC1 cell stemness contribute to enhanced malignant tumor properties in murine models of sleep apnea. Sleep. https://doi.org/10.1093/sleep/zsw040 CrossRef

42.

Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 49(11):1603–1616CrossRefPubMedPubMedCentral

43.

Hatfield SM, Kjaergaard J, Lukashev D et al (2015) Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci Transl Med 7(277):277ra30. https://doi.org/10.1126/scitranslmed.aaa1260 CrossRefPubMedCentralPubMed

44.

Gharib SA, Seiger AN, Hayes AL, Mehra R, Patel SR (2014) Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes. Sleep 37(4):709–714, 714A–714T. https://doi.org/10.5665/sleep.3574 CrossRefPubMedCentralPubMed

45.

Ryan HE, Poloni M, McNulty W et al (2000) Hypoxia-inducible factor-1alpha is a positive factor in solid tumor growth. Cancer Res 60(15):4010–4015PubMed

46.

Dewhirst MW (2007) Intermittent hypoxia furthers the rationale for hypoxia-inducible factor-1 targeting. Cancer Res 67(3):854–855CrossRefPubMed

47.

Wang JQ, Jeelall YS, Ferguson LL, Horikawa K (2014) Toll-like receptors and cancer: MYD88 mutation and inflammation. Front Immunol 5:367. https://doi.org/10.3389/fimmu.2014.00367 CrossRefPubMedCentralPubMed

48.

Madonna G, Ullman CD, Gentilcore G, Palmieri G, Ascierto PA (2012) NF-κB as potential target in the treatment of melanoma. J Transl Med 10(1):53CrossRefPubMedPubMedCentral

49.

Li S, Qian X, Zhou W et al (2011) Time-dependent inflammatory factor production and NFκB activation in a rodent model of intermittent hypoxia. Swiss Med Wkly 141:w13309PubMed

50.

Gudas LJ, Fu L, Minton DR, Mongan NP, Nanus DM (2014) The role of HIF1α in renal cell carcinoma tumorigenesis. J Mol Med 92(8):825–836CrossRefPubMed

51.

Zhang XB, Peng LH, Lyu Z, Jiang XT, Du YP (2017) Obstructive sleep apnoea and the incidence and mortality of cancer: a meta-analysis. Eur J Cancer Care 26(2):e12427CrossRef

52.

Shantha GPS, Kumar AA, Cheskin LJ, Pancholy SB (2015) Association between sleep-disordered breathing, obstructive sleep apnea, and cancer incidence: a systematic review and meta-analysis. Sleep Med 16(10):1289–1294CrossRef

53.

Martinez-Garcia MA, Campos-Rodriguez F, Barbe F (2016) Cancer and OSA: current evidence from human studies. Chest 150(2):451–463. https://doi.org/10.1016/j.chest.2016.04.029 CrossRefPubMed

54.

Martinez-Garcia M, Campos-Rodriguez F, Nagore E et al (2018) Sleep-disordered breathing is independently associated with increased aggressiveness of cutaneous melanoma. A multicentre observational study in 443 patients. Chest. https://doi.org/10.1016/j.chest.2018.07.015 CrossRefPubMed

55.

Torres M, Campillo N, Nonaka PN et al (2018) Aging reduces intermittent hypoxia-induced lung carcinoma growth in a mouse model of sleep apnea. Am J Respir Crit Care Med

56.

Wang F, Xu Y (2014) Body mass index and risk of renal cell cancer: a dose-response meta-analysis of published cohort studies. Int J Cancer 135(7):1673–1686CrossRefPubMed

57.

Genkinger JM, Spiegelman D, Anderson KE et al (2011) A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int J Cancer 129(7):1708–1717CrossRefPubMedPubMedCentral

58.

Munsell MF, Sprague BL, Berry DA, Chisholm G, Trentham-Dietz A (2014) Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status. Epidemiol Rev 36(1):114–136CrossRefPubMedPubMedCentral

59.

Schwartz AR, Patil SP, Laffan AM, Polotsky V, Schneider H, Smith PL (2008) Obesity and obstructive sleep apnea: pathogenic mechanisms and therapeutic approaches. Proc Am Thorac Soc 5(2):185–192CrossRef

60.

Shipman A, Millington G (2011) Obesity and the skin. Br J Dermatol 165(4):743–750CrossRefPubMed

61.

Bjørge T, Engeland A, Tretli S, Weiderpass E (2007) Body size in relation to cancer of the uterine corpus in 1 million norwegian women. Int J Cancer 120(2):378–383CrossRefPubMed

62.

Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L (2014) Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet 384(9945):755–765CrossRefPubMedPubMedCentral

63.

Shi Y, Hu FB (2014) The global implications of diabetes and cancer. Lancet 383(9933):1947–1948. https://doi.org/10.1016/S0140-6736(14)60886-2 CrossRefPubMed

64.

https://www.doh.wa.gov/portals/1/documents/pubs/345-271-ChronicDiseaseProfileKing.pdf. Accessed 20 Feb 2018

Title: Sleep apnea and subsequent cancer incidence
Authors: Arthur Sillah
Nathaniel F. Watson
Stephen M. Schwartz
David Gozal
Amanda I. Phipps
Publication date: 01-10-2018
Publisher: Springer International Publishing
Published in: Cancer Causes & Control / Issue 10/2018
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI: https://doi.org/10.1007/s10552-018-1073-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 10/2018

Intersectional nativity and racial/ethnic disparities in human papillomavirus vaccination initiation among U.S. women: a national population-based study

Temporal reliability of serum soluble and endogenous secretory receptors for advanced glycation end-products (sRAGE and esRAGE) in healthy women

The relationship between diabetes, prostate-specific antigen screening tests, and prostate cancer

Indoor tanning and the risk of developing non-cutaneous cancers: a systematic review and meta-analysis

Review of non-clinical risk models to aid prevention of breast cancer

Childhood diet and growth in boys in relation to timing of puberty and adult height: the Longitudinal Studies of Child Health and Development

Keynote webinar | Spotlight on antibody–drug conjugates in cancer