Sleep Apnoea Adverse Effects on Cancer: True, False, or Too Many Confounders?

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Nov 25

PMID 33233617

Citations 17

Authors

David Gozal

Isaac Almendros

Amanda I Phipps

Francisco Campos-Rodriguez

Miguel A Martinez-Garcia

Ramon Farre

Affiliations

Soon will be listed here.

Abstract

Obstructive sleep apnoea (OSA) is a prevalent disorder associated with increased cardiovascular, metabolic and neurocognitive morbidity. Recently, an increasing number of basic, clinical and epidemiological reports have suggested that OSA may also increase the risk of cancer, and adversely impact cancer progression and outcomes. This hypothesis is convincingly supported by biological evidence linking certain solid tumours and hypoxia, as well as by experimental studies involving cell and animal models testing the effects of intermittent hypoxia and sleep fragmentation that characterize OSA. However, the clinical and epidemiological studies do not conclusively confirm that OSA adversely affects cancer, even if they hold true for specific cancers such as melanoma. It is likely that the inconclusive studies reflect that they were not specifically designed to test the hypothesis or because of the heterogeneity of the relationship of OSA with different cancer types or even sub-types. This review critically focusses on the extant basic, clinical, and epidemiological evidence while formulating proposed directions on how the field may move forward.

Citing Articles

Long-term incident severe outcomes in a prospective cohort of non-obese obstructive sleep apnoea patients free of comorbidities at inclusion.

Briancon-Marjollet A, Joyeux-Faure M, Ben Messaoud R, Bailly S, NGo V, Colombet S ERJ Open Res. 2024; 10(4).

PMID: 38978551 PMC: 11228602. DOI: 10.1183/23120541.00930-2023.

Impact of sleep on gastrointestinal cancer.

Lo J, Taweesedt P, Kawai M World J Clin Oncol. 2024; 15(6):677-683.

PMID: 38946837 PMC: 11212604. DOI: 10.5306/wjco.v15.i6.677.

Risk of cancer in patients with sleep apnea: comparison of surgery versus CPAP in a long-term follow-up study.

OConnor-Reina C, Rodriguez Alcala L, Ignacio J, Garcia-Iriarte M, Carrasco Llatas M, Casado Morente J Eur Arch Otorhinolaryngol. 2024; 281(6):3131-3141.

PMID: 38206392 DOI: 10.1007/s00405-023-08446-3.

Multi-Omics Analysis of Circulating Exosomes in Adherent Long-Term Treated OSA Patients.

Khalyfa A, Marin J, Sanz-Rubio D, Lyu Z, Joshi T, Gozal D Int J Mol Sci. 2023; 24(22).

PMID: 38003263 PMC: 10671639. DOI: 10.3390/ijms242216074.

Cancer and Obesity: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022.

Lazarus E, Bays H Obes Pillars. 2023; 3:100026.

PMID: 37990728 PMC: 10661911. DOI: 10.1016/j.obpill.2022.100026.

References

Gao J, Cao H, Zhang Q, Wang B . The effect of intermittent hypoxia and fecal microbiota of OSAS on genes associated with colorectal cancer. Sleep Breath. 2020; 25(2):1075-1087. PMC: 8195781. DOI: 10.1007/s11325-020-02204-z. View

Jara S, Phipps A, Maynard C, Weaver E . The Association of Sleep Apnea and Cancer in Veterans. Otolaryngol Head Neck Surg. 2020; 162(4):581-588. DOI: 10.1177/0194599819900487. View

Saxena K, Jolly M . Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression. Biomolecules. 2019; 9(8). PMC: 6722594. DOI: 10.3390/biom9080339. View

Yoon D, Kim Y, Hwang S, Khalmuratova R, Lee M, Kim J . Intermittent hypoxia promotes carcinogenesis in azoxymethane and dextran sodium sulfate-induced colon cancer model. Mol Carcinog. 2018; 58(5):654-665. DOI: 10.1002/mc.22957. View

Zheng J, Almendros I, Wang Y, Zhang S, Carreras A, Qiao Z . Reduced NADPH oxidase type 2 activity mediates sleep fragmentation-induced effects on TC1 tumors in mice. Oncoimmunology. 2015; 4(2):e976057. PMC: 4404846. DOI: 10.4161/2162402X.2014.976057. View

Cohen J, Li Y, Wu S, Han J, Qureshi A, Cho E . Sleep duration and sleep-disordered breathing and the risk of melanoma among US women and men. Int J Dermatol. 2015; 54(11):e492-5. PMC: 4609230. DOI: 10.1111/ijd.12904. View

Nieto F, Peppard P, Young T, Finn L, Hla K, Farre R . Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study. Am J Respir Crit Care Med. 2012; 186(2):190-4. PMC: 3406081. DOI: 10.1164/rccm.201201-0130OC. View

Vaupel P, Mayer A . Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007; 26(2):225-39. DOI: 10.1007/s10555-007-9055-1. View

Phipps A, Bhatti P, Neuhouser M, Chen C, Crane T, Kroenke C . Pre-diagnostic Sleep Duration and Sleep Quality in Relation to Subsequent Cancer Survival. J Clin Sleep Med. 2015; 12(4):495-503. PMC: 4795275. DOI: 10.5664/jcsm.5674. View

10.

Gallego-Martin T, Farre R, Almendros I, Gonzalez-Obeso E, Obeso A . Chronic intermittent hypoxia mimicking sleep apnoea increases spontaneous tumorigenesis in mice. Eur Respir J. 2017; 49(2). DOI: 10.1183/13993003.02111-2016. View

11.

Cubillos-Zapata C, Balbas-Garcia C, Avendano-Ortiz J, Toledano V, Torres M, Almendros I . Age-dependent hypoxia-induced PD-L1 upregulation in patients with obstructive sleep apnoea. Respirology. 2019; 24(7):684-692. DOI: 10.1111/resp.13470. View

12.

Martinez C, Kerr B, Jin C, Cistulli P, Cook K . Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells. Int J Mol Sci. 2019; 20(2). PMC: 6359625. DOI: 10.3390/ijms20020445. View

13.

Cortese R, Almendros I, Wang Y, Gozal D . Tumor circulating DNA profiling in xenografted mice exposed to intermittent hypoxia. Oncotarget. 2014; 6(1):556-69. PMC: 4381615. DOI: 10.18632/oncotarget.2785. View

14.

Kendzerska T, Leung R, Hawker G, Tomlinson G, Gershon A . Obstructive sleep apnea and the prevalence and incidence of cancer. CMAJ. 2014; 186(13):985-92. PMC: 4162778. DOI: 10.1503/cmaj.140238. View

15.

Campillo N, Torres M, Vilaseca A, Nonaka P, Gozal D, Roca-Ferrer J . Role of Cyclooxygenase-2 on Intermittent Hypoxia-Induced Lung Tumor Malignancy in a Mouse Model of Sleep Apnea. Sci Rep. 2017; 7:44693. PMC: 5353645. DOI: 10.1038/srep44693. View

16.

Choi J, Kim S, Han K, Cho J . The incidence of non-Hodgkin lymphoma is increased in patients with obstructive sleep apnea. Leuk Res. 2020; 98:106455. DOI: 10.1016/j.leukres.2020.106455. View

17.

Chao Y, Shang J, Ji W . ALKBH5-mA-FOXM1 signaling axis promotes proliferation and invasion of lung adenocarcinoma cells under intermittent hypoxia. Biochem Biophys Res Commun. 2019; 521(2):499-506. DOI: 10.1016/j.bbrc.2019.10.145. View

18.

Torres M, Martinez-Garcia M, Campos-Rodriguez F, Gozal D, Montserrat J, Navajas D . Lung cancer aggressiveness in an intermittent hypoxia murine model of postmenopausal sleep apnea. Menopause. 2020; 27(6):706-713. DOI: 10.1097/GME.0000000000001526. View

19.

Campos-Rodriguez F, Cruz-Medina A, Selma M, Rodriguez-de-la-Borbolla-Artacho M, Sanchez-Vega A, Ripoll-Orts F . Association between sleep-disordered breathing and breast cancer aggressiveness. PLoS One. 2018; 13(11):e0207591. PMC: 6248981. DOI: 10.1371/journal.pone.0207591. View

20.

Gozal D, Farre R, Nieto F . Obstructive sleep apnea and cancer: Epidemiologic links and theoretical biological constructs. Sleep Med Rev. 2015; 27:43-55. PMC: 5374514. DOI: 10.1016/j.smrv.2015.05.006. View