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

Gozal, David; Almendros, Isaac; Phipps, Amanda I.; Campos‐Rodríguez, Francisco; Martínez‐García, Miguel Ángel; Farré, Ramón

doi:10.3390/ijms21228779

Cited by 36 publications

(30 citation statements)

References 91 publications

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“…These data raise several issues both at clinical and preclinical levels. Indeed, the association between OSA and cancer patients' outcome remains an open issue since there are many other confounding risk factors, which could affect prognosis [ 15 ]. Patients affected by OSA are often affected by obesity, which may contribute to chronic inflammation, altering the balance between oxidative stress, hormones, growth factors, and other mediators.…”

Section: Discussionmentioning

confidence: 99%

“…Patients affected by OSA are often affected by obesity, which may contribute to chronic inflammation, altering the balance between oxidative stress, hormones, growth factors, and other mediators. Furthermore, several other confounding factors, such as cardiologic and metabolic comorbidities, besides cancer, may affect patient outcome [ 15 ]. In such a perspective, our data, obtained in a small, but homogeneous cohort of mCRCs, support the hypothesis that OSA may represent an independent predictor of poor response to standard first-line therapy and may negatively impact on cancer-specific survival.…”

Section: Discussionmentioning

confidence: 99%

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Obstructive Sleep Apnea Worsens Progression-Free and Overall Survival in Human Metastatic Colorectal Carcinoma

Lacedonia

Landriscina

Scioscia

et al. 2021

Journal of Oncology

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Sleep disorders have emerged as highly prevalent conditions, and along with improved understanding of such disorders, increased attention has gained the evidence that perturbation in sleep architecture and continuity may initiate, exacerbate, or modulate the phenotypic expression of multiple diseases including cancer. Furthermore, obstructive sleep apnea (OSA) has recently been implicated in increased incidence and more adverse prognosis of cancer in humans. This study was designed to confirm the high prevalence of OSA in human malignancies and assess its prognostic relevance in metastatic colorectal carcinomas (mCRCs). A prospective cohort of 52 subjects, affected by solid histologically confirmed metastatic malignancies, was analyzed, and among them, 29 mCRCs were studied for the prognostic role of OSA. OSA was diagnosed in 34.6% (18/52) of patients with a statistically significant difference in apnea-hyponea index between OSA and non-OSA subgroups (14.2 ± 12.2 vs. 2.1 ± 1.5, p < 0.01 ). Consistently, OSA was diagnosed in 34.5% (10/29) of mCRCs with lower rates of first-line therapy disease control in OSA compared to non-OSA patients (60% in OSA vs. 94.7% in non-OSA, p = 0.03 ). Of note, progression-free and overall survival rates were significantly shorter in OSA (respectively, 9 and 22 months) compared non-OSA (20 and 40 months) mCRC patients (HR = 2.63; 95% CI 0.88–7.84, p = 0.01 for PFS; HR = 3.93; 95% CI 1.13–13.73, p < 0.001 for OS). Finally, the multivariate analysis showed that OSA is an independent prognostic factor for PFS p = 0.0076 and OS p = 0.0017 in this cohort. Altogether, these data suggest that OSA is a potential clinical marker predictor of poor prognosis in patients with mCRC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Obstructive Sleep Apnea Worsens Progression-Free and Overall Survival in Human Metastatic Colorectal Carcinoma

Lacedonia

Landriscina

Scioscia

et al. 2021

Journal of Oncology

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“…In fact, SDs increase the risk of insulin-resistance, obesity, and diabetes mellitus (DM) ( 15 ), and intermittent hypoxemia in OSA is an independent risk factor for cardiovascular and cardiorespiratory mortality ( 16 ). SDs may also represent a risk factor for neurocognitive decline ( 17 ) and cancer ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Sleep Disorders in Patients With Craniopharyngioma: A Physiopathological and Practical Update

et al. 2022

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Sleep disorders (SDs) represent an important issue in patients with craniopharyngioma (CP). Nearly 70% of these patients complain of sleep-wake cycle alterations and/or excessive diurnal somnolence due to sleep-related breathing disorders, such as obstructive sleep apnea (OSA) and/or central hypersomnia, including secondary narcolepsy. SDs may severely reduce quality of life, increase disease-related cardiorespiratory and cardiovascular morbidity, and finally play a major role in increased long-term mortality reported on patients with CP. A major risk factor for SDs is represented by the hypothalamic syndrome, which may develop because of direct hypothalamic damage by the tumor itself and/or complications of the treatments, neurosurgery and/or radiotherapy, and typically includes permanent neuroendocrine dysfunctions, morbid obesity, and secondary metabolic disorders. Despite increasing attention to SDs in the general population, and in particular to OSA as a risk factor for cardio-metabolic diseases and excessive daytime somnolence, sleep evaluation is still not routinely proposed to patients with CP. Hence, SDs are often underdiagnosed and undertreated. The aim of this paper is to update current knowledge of the pathogenesis and prevalence of SDs in patients with CP and propose practical algorithms for their evaluation and management in clinical practice. Particular attention is paid to screening and diagnostic tools for appropriate characterization of SDs, identification of risk factors, and potential role of hypothalamic sparing surgery in the prevention of morbid obesity and SDs. Available tools in sleep medicine, including lifestyle interventions, drugs, and respiratory devices, are discussed, as well as the importance of optimal hormone replacement and metabolic interventions. Current limits in the diagnosis and treatment of SDs in patients with CP and possible future avenues for research agenda are also considered.

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“…Importantly, clinical and epidemiological reports suggest that OSA is independently associated with an increased risk of all-cause mortality, including cancer mortality [2,3]. In particular, studies focused on the impact of chronic intermittent hypoxia on cancer progression and clinical outcome have been gaining considerable attention [4,5]. The results from animal studies revealed that intermittent hypoxia promotes melanoma [6,7] and lung tumor progression [8] and increases the risk of a metastatic phenotype in breast cancer [9].…”

Section: Introductionmentioning

confidence: 99%

Chronic Intermittent Hypoxia Increases Cell Proliferation in Hepatocellular Carcinoma

Carreres

Mercey-Ressejac

Kurma

et al. 2022

Cells

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Obstructive sleep apnea (OSA) syndrome is characterized by chronic intermittent hypoxia and is associated with an increased risk of all-cause mortality, including cancer mortality. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, characterized by increasing incidence and high mortality. However, the link between HCC and OSA-related chronic intermittent hypoxia remains unclear. Herein, we used a diethylnitrosamine (DEN)-induced HCC model to investigate whether OSA-related chronic intermittent hypoxia has an impact on HCC progression. To elucidate the associated mechanisms, we first evaluated the hypoxia status in the DEN-induced HCC model. Next, to simulate OSA-related intermittent hypoxia, we exposed cirrhotic rats with HCC to intermittent hypoxia during six weeks. We performed histopathological, immunohistochemical, RT-qPCR, and RNA-seq analysis. Chronic DEN injections strongly promoted cell proliferation, fibrosis, disorganized vasculature, and hypoxia in liver tissue, which mimics the usual events observed during human HCC development. Intermittent hypoxia further increased cell proliferation in DEN-induced HCC, which may contribute to an increased risk of HCC progression. In conclusion, our observations suggest that chronic intermittent hypoxia may be a factor worsening the prognosis of HCC.

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

Cited by 36 publications

References 91 publications

Obstructive Sleep Apnea Worsens Progression-Free and Overall Survival in Human Metastatic Colorectal Carcinoma

Obstructive Sleep Apnea Worsens Progression-Free and Overall Survival in Human Metastatic Colorectal Carcinoma

Sleep Disorders in Patients With Craniopharyngioma: A Physiopathological and Practical Update

Chronic Intermittent Hypoxia Increases Cell Proliferation in Hepatocellular Carcinoma

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