Intermittent hypoxia enhances cancer progression in a mouse model of sleep apnoea

Almendros, Isaac; Montserrat, Josep M.; Ramírez, Josep; Torres, Marta; Durán-Cantolla, Joaquín; Navajas, Daniel; Farré, Ramón

doi:10.1183/09031936.00185110

Cited by 197 publications

(161 citation statements)

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“…Cancer cells subjected to either chronic (8)(9)(10) or intermittent hypoxia (11) show increased resistance to therapy (e.g., radiation) and malignant progression. Furthermore, recent experiments in a melanoma-injected mouse model demonstrate that intermittent hypoxia mimicking sleep apnea in humans increases tumor growth (12). This association might be explained by the increased angiogenesis associated with tissue hypoxemia (13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sleep-disordered Breathing and Cancer Mortality

Nieto¹,

Peppard²,

Young³

et al. 2012

Am J Respir Crit Care Med

400

139

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Rationale: Sleep-disordered breathing (SDB) has been associated with total and cardiovascular mortality, but an association with cancer mortality has not been studied. Results from in vitro and animal studies suggest that intermittent hypoxia promotes cancer tumor growth. Objectives: The goal of the present study was to examine whether SDB is associated with cancer mortality in a community-based sample. Methods: We used 22-year mortality follow-up data from the Wisconsin Sleep Cohort sample (n ¼ 1,522). SDB was assessed at baseline with full polysomnography. SDB was categorized using the apnea-hypopnea index (AHI) and the hypoxemia index (percent sleep time below 90% oxyhemoglobin saturation). The hazards of cancer mortality across levels of SDB severity were compared using crude and multivariate analyses. Measurements and Main Results: Adjusting for age, sex, body mass index, and smoking, SDB was associated with total and cancer mortality in a dose-response fashion. Compared with normal subjects, the adjusted relative hazards of cancer mortality were 1.1 (95% confidence interval [CI], 0.5-2.7) for mild SDB (AHI, 5-14.9), 2.0 (95% CI, 0.7-5.5) for moderate SDB (AHI, 15-29.9), and 4.8 (95% CI, 1.7-13.2) for severe SDB (AHI > 30) (P-trend ¼ 0.0052). For categories of increasing severity of the hypoxemia index, the corresponding relative hazards were 1.6 (95% CI, 0.6-4.4), 2.9 (95% CI, 0.9-9.8), and 8.6 (95% CI, 2.6-28.7). Conclusions: Our study suggests that baseline SDB is associated with increased cancer mortality in a community-based sample. Future studies that replicate our findings and look at the association between sleep apnea and survival after cancer diagnosis are needed.Keywords: cancer; cohort study; mortality; obstructive sleep apnea; sleep-disordered breathing Sleep disordered breathing (SDB) is characterized by recurrent episodes of total or partial obstruction of the upper airway (apnea or hypopnea) during sleep that are associated with intermittent hypoxemia, repeated sleep disruption, and snoring (1). The prevalence of moderate to severe SDB has been estimated to be as high as 6% among U.S. adults and rising as the prevalence of obesity, a major risk factor for SDB, continues to increase (2-4). SDB is associated with a variety of psychopathological disorders (depression, reduced quality of life) and increased risk of occupational and motor vehicle injuries, as well as with a variety of cardiovascular disease outcomes, hypertension, and the metabolic syndrome (3, 5, 6). These associations have been explained by the profound metabolic and sympathetic system disruption associated with repeated hypoxemic events (6, 7).Chronic hypoxia, a common feature in solid tumor tissue, has been associated with therapeutic resistance, tumor progression, and metastatic potential (8-10). In vitro studies have further demonstrated that cultured lung cancer cells subject to intermittent hypoxia are more resistant to radiation and apoptosis and are more prone to metastasis (11).Recent results from a study using a mouse...

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Section: Discussionmentioning

confidence: 99%

“…Recent results from a study using a mouse model for obstructive sleep apnea showed that intermittent hypoxia was associated with accelerated cancer progression (12). These effects might be mediated by the hypoxia-induced increased tumor tissue angiogenesis and resulting cell proliferation and tumor growth (13)(14)(15).…”

mentioning

confidence: 99%

Sleep-disordered Breathing and Cancer Mortality

Nieto¹,

Peppard²,

Young³

et al. 2012

Am J Respir Crit Care Med

400

139

View full text Add to dashboard Cite

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“…A possible link between SAS and cancer has recently been suggested [55,56] and possible involvements of vascular endothelial growth factor, hypoxia-inducible factor, and reactive oxygen species-activated activator protein 1 and nuclear factor-κB in cancer development/ progression in SAS patients were reported [57]. Recently, enhanced metastatic ability of IH-treated human pancreatic cancer cell lines (PANC-1 and BxPC-3) was also reported [58].…”

Section: Hepatocyte Growth Factor (Hgf) Gene Expression Was Increasedmentioning

confidence: 99%

Intermittent Hypoxia in Pancreatic beta Cells

Ota¹,

Takasawa²,

Yamauchi³

et al. 2015

Pancreat Disord Ther

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Sleep apnea syndrome (SAS) a highly prevalent disorder, and characterized by repetitive episodes of intermittent hypoxia (IH), i.e. recurrent episodes of oxygen desaturation during sleep, the development of daytime sleepiness, and deterioration in the quality of life. Multiple epidemiological studies have provided evidence implicating the presence of SAS as a risk factor for insulin resistance and type 2 diabetes and have reported that type 2 diabetes is associated with SAS independently of age, sex, and body habitus. One of the postulated mechanisms for the metabolic alterations associated with SAS is that IH leads to substantial alterations in both pancreatic β cell function and organ glucose homeostasis. On the other hand, hyperglycemia is known to increase the rate of β cell replication, which can provide an increased source of insulin to combat insulin resistance. Although accumulating evidence suggests associations between SAS and type 2 diabetes, the direct effect of IH on pancreatic β cell has been unknown. In this review, we focus on the impact of IH on pancreatic β cells, particularly β cell dysfunction and cell proliferation.

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“…Experimental and clinical studies have suggested a potential relationship between OSA and cancer development or progression (1,2). Epidemiological evidence from relatively small cohorts suggests that OSA is associated with higher cancer incidence and mortality, mainly in patients with severe sleep-disordered breathing.…”

Section: Update From the European Sleep Apnea Database (Esada) On Canmentioning

confidence: 99%