Skip to main content
Erschienen in: World Journal of Urology 1/2017

23.04.2016 | Original Article

Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically

verfasst von: Antoni Vilaseca, Daniel P. Nguyen, Emily A. Vertosick, Renato B. Corradi, Mireia Musquera, Meritxell Pérez, Nicola Fossati, Daniel D. Sjoberg, Ramon Farré, Isaac Almendros, Josep M. Montserrat, Nicole E. Benfante, A. Ari Hakimi, Anders J. Skanderup, Paul Russo, Antonio Alcaraz, Karim A. Touijer

Erschienen in: World Journal of Urology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To assess the association between obstructive sleep apnea (OSA) and Fuhrman grade in patients with clear cell renal cell carcinoma (ccRCC). As secondary endpoints, we studied its association with tumor size, metastasis-free survival (MFS) and cancer-specific survival (CSS).

Methods

We reviewed the databases of two tertiary care centers, identifying 2579 patients who underwent partial or radical nephrectomy for ccRCC between 1991 and 2014. Descriptive statistics were used to compare pathologic variables between patients with and without OSA. Linear and logistic regression models were used to assess the association of OSA with Fuhrman grade and tumor size. A Cox proportional hazards model was used to determine OSA association with MFS and CSS. A pathway analysis was performed on a cohort with available gene expression data.

Results

In total, 172 patients (7 %) had self-reported OSA at diagnosis. More patients with OSA had high Fuhrman grade compared to those without OSA [51 vs. 38 %; 13 % risk difference; 95 % confidence interval (CI), 5–20 %; p = 0.003]. On multivariable analysis, the association remained significant (OR 1.41; 95 % CI 1.00–1.99; p = 0.048). OSA was not associated with tumor size (p > 0.5), MFS (p = 0.5) or CSS (p = 0.4). A trend toward vascular endothelial growth factor pathway enrichment was seen in OSA patients (p = 0.08).

Conclusions

OSA is associated with high Fuhrman grade in patients undergoing surgery for ccRCC. Pending validation of this novel finding in further prospective studies, it could help shape future research to better understand etiological mechanisms associated.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Malhotra A, White DP (2012) Obstructive sleep apnoea. Lancet 360:237–245CrossRef Malhotra A, White DP (2012) Obstructive sleep apnoea. Lancet 360:237–245CrossRef
3.
Zurück zum Zitat Levy P, Godin-Ribuot D, Pepin JL (2014) Sleep apnoea and cancer: the new challenge. Eur Respir J 43:1567–1570CrossRefPubMed Levy P, Godin-Ribuot D, Pepin JL (2014) Sleep apnoea and cancer: the new challenge. Eur Respir J 43:1567–1570CrossRefPubMed
4.
Zurück zum Zitat 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. Am J Respir Crit Care Med 187:99–105CrossRefPubMed 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. Am J Respir Crit Care Med 187:99–105CrossRefPubMed
5.
Zurück zum Zitat Martinez-Garcia MA, Martorell-Calatayud A, Nagore E et al (2014) Association between sleep disordered breathing and aggressiveness markers of malignant cutaneous melanoma. Eur Respir J 43:1661–1668CrossRefPubMed Martinez-Garcia MA, Martorell-Calatayud A, Nagore E et al (2014) Association between sleep disordered breathing and aggressiveness markers of malignant cutaneous melanoma. Eur Respir J 43:1661–1668CrossRefPubMed
6.
Zurück zum Zitat 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. Am J Respir Crit Care Med 186:190–194CrossRefPubMedPubMedCentral 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. Am J Respir Crit Care Med 186:190–194CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Almendros I, Montserrat JM, Ramirez J, Torres M, Duran-Cantolla J, Navajas D, Farré R (2012) Intermittent hypoxia enhances cancer progression in a mouse model of sleep apnoea. Eur Respir J 39:215–217CrossRefPubMed Almendros I, Montserrat JM, Ramirez J, Torres M, Duran-Cantolla J, Navajas D, Farré R (2012) Intermittent hypoxia enhances cancer progression in a mouse model of sleep apnoea. Eur Respir J 39:215–217CrossRefPubMed
8.
Zurück zum Zitat Almendros I, Montserrat JM, Torres M et al (2013) Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea. Respir Physiol Neurobiol 186:303–307CrossRefPubMed Almendros I, Montserrat JM, Torres M et al (2013) Intermittent hypoxia increases melanoma metastasis to the lung in a mouse model of sleep apnea. Respir Physiol Neurobiol 186:303–307CrossRefPubMed
9.
Zurück zum Zitat Almendros I, Montserrat JM, Torres M, Bonsignore MR, Chimenti L, Navajas D, Farré R (2012) Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea. Sleep Med 13:1254–1260CrossRefPubMed Almendros I, Montserrat JM, Torres M, Bonsignore MR, Chimenti L, Navajas D, Farré R (2012) Obesity and intermittent hypoxia increase tumor growth in a mouse model of sleep apnea. Sleep Med 13:1254–1260CrossRefPubMed
10.
Zurück zum Zitat Gudas LJ, Fu L, Minton DR, Mongan NP, Nanus DM (2014) The role of HIF1α in renal cell carcinoma tumorigenesis. J Mol Med (Berl) 92:825–836CrossRef Gudas LJ, Fu L, Minton DR, Mongan NP, Nanus DM (2014) The role of HIF1α in renal cell carcinoma tumorigenesis. J Mol Med (Berl) 92:825–836CrossRef
11.
Zurück zum Zitat Toth K, Chintala S, Rustum YM (2014) Constitutive expression of HIF-α plays a major role in generation of clear-cell phenotype in human primary and metastatic renal carcinoma. Appl Immunohistochem Mol Morphol 22:642–647CrossRefPubMedPubMedCentral Toth K, Chintala S, Rustum YM (2014) Constitutive expression of HIF-α plays a major role in generation of clear-cell phenotype in human primary and metastatic renal carcinoma. Appl Immunohistochem Mol Morphol 22:642–647CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Patard JJ, Rioux-Leclercq N, Fergelot P (2006) Understanding the importance of smart drugs in renal cell carcinoma. Eur Urol 49:633–643CrossRefPubMed Patard JJ, Rioux-Leclercq N, Fergelot P (2006) Understanding the importance of smart drugs in renal cell carcinoma. Eur Urol 49:633–643CrossRefPubMed
13.
Zurück zum Zitat Shoji S, Nakano M, Sato H et al (2014) The current status of tailor-made medicine with molecular biomarkers for patients with clear cell renal cell carcinoma. Clin Exp Metastasis 31:111–134CrossRefPubMed Shoji S, Nakano M, Sato H et al (2014) The current status of tailor-made medicine with molecular biomarkers for patients with clear cell renal cell carcinoma. Clin Exp Metastasis 31:111–134CrossRefPubMed
14.
Zurück zum Zitat Greene FL, Page D, Flemming I et al (2002) AJCC cancer staging manual, 6th edn. Springer, New YorkCrossRef Greene FL, Page D, Flemming I et al (2002) AJCC cancer staging manual, 6th edn. Springer, New YorkCrossRef
15.
Zurück zum Zitat Creighton CJ, Morgan M, Gunaratne PH et al (2013) Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499(7456):43–49CrossRef Creighton CJ, Morgan M, Gunaratne PH et al (2013) Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499(7456):43–49CrossRef
16.
Zurück zum Zitat Subramanian A, Tamayo P, Mootha VK et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550CrossRefPubMedPubMedCentral Subramanian A, Tamayo P, Mootha VK et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Li C, Ford ES, Zhao G, Croft JB, Balluz LS, Mokdad AH (2010) Prevalence of self-reported clinically diagnosed sleep apnea according to obesity status in men and women: National Health and Nutrition Examination Survey, 2005–2006. Prev Med 51:18–23CrossRefPubMed Li C, Ford ES, Zhao G, Croft JB, Balluz LS, Mokdad AH (2010) Prevalence of self-reported clinically diagnosed sleep apnea according to obesity status in men and women: National Health and Nutrition Examination Survey, 2005–2006. Prev Med 51:18–23CrossRefPubMed
18.
Zurück zum Zitat Fuhrman SA, Lasky LC, Limas C (1982) Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 6:655–663CrossRefPubMed Fuhrman SA, Lasky LC, Limas C (1982) Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 6:655–663CrossRefPubMed
19.
Zurück zum Zitat Raj GV, Thompson RH, Leibovich BC, Blute ML, Russo P, Kattan MW (2008) Preoperative nomogram predicting 12-year probability of metastatic renal cancer. J Urol 179:2146–2151CrossRefPubMedPubMedCentral Raj GV, Thompson RH, Leibovich BC, Blute ML, Russo P, Kattan MW (2008) Preoperative nomogram predicting 12-year probability of metastatic renal cancer. J Urol 179:2146–2151CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Hakimi AA, Furberg H, Zabor EC et al (2013) An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Cancer Inst 105:1862–1870CrossRefPubMedPubMedCentral Hakimi AA, Furberg H, Zabor EC et al (2013) An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Cancer Inst 105:1862–1870CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Almendros I, Wang Y, Becker L et al (2014) Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. Am J Respir Crit Care Med 189:593–601CrossRefPubMedPubMedCentral Almendros I, Wang Y, Becker L et al (2014) Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. Am J Respir Crit Care Med 189:593–601CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Hakim F, Wang Y, Zhang SXL et al (2014) Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res 74:1329–1337CrossRefPubMedPubMedCentral Hakim F, Wang Y, Zhang SXL et al (2014) Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res 74:1329–1337CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Ohh M, Park CW, Ivan M et al (2000) Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel–Lindau protein. Nat Cell Biol 2:423–427CrossRefPubMed Ohh M, Park CW, Ivan M et al (2000) Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel–Lindau protein. Nat Cell Biol 2:423–427CrossRefPubMed
24.
Zurück zum Zitat Kaelin WG Jr (2007) The von Hippel–Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res 13:680s–684sCrossRefPubMed Kaelin WG Jr (2007) The von Hippel–Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res 13:680s–684sCrossRefPubMed
26.
Zurück zum Zitat Yuan G, Nanduri J, Khan S, Semenza GL, Prabhakar NR (2008) Induction of HIF-1α expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J Cell Physiol 217:674–685CrossRefPubMedPubMedCentral Yuan G, Nanduri J, Khan S, Semenza GL, Prabhakar NR (2008) Induction of HIF-1α expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J Cell Physiol 217:674–685CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Schulz R, Hummel C, Heinemann S, Seeger W, Grimminger F (2002) Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia. Am J Respir Crit Care Med 165:67–70CrossRefPubMed Schulz R, Hummel C, Heinemann S, Seeger W, Grimminger F (2002) Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia. Am J Respir Crit Care Med 165:67–70CrossRefPubMed
28.
Zurück zum Zitat Marshall NS, Wong KKH, Liu PY, Cullen SRJ, Knuiman MW, Grunstein RR (2008) Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. Sleep 31(8):1079–1085PubMedPubMedCentral Marshall NS, Wong KKH, Liu PY, Cullen SRJ, Knuiman MW, Grunstein RR (2008) Sleep apnea as an independent risk factor for all-cause mortality: the Busselton Health Study. Sleep 31(8):1079–1085PubMedPubMedCentral
29.
Zurück zum Zitat Marin JM, Carrizo SJ, Vicente E, Agusti AG (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea–hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365:1046–1053CrossRefPubMed Marin JM, Carrizo SJ, Vicente E, Agusti AG (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea–hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365:1046–1053CrossRefPubMed
30.
Zurück zum Zitat Marin JM, Agusti A, Villar I et al (2012) Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 307(20):2169–2176CrossRefPubMedPubMedCentral Marin JM, Agusti A, Villar I et al (2012) Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 307(20):2169–2176CrossRefPubMedPubMedCentral
Metadaten
Titel
Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically
verfasst von
Antoni Vilaseca
Daniel P. Nguyen
Emily A. Vertosick
Renato B. Corradi
Mireia Musquera
Meritxell Pérez
Nicola Fossati
Daniel D. Sjoberg
Ramon Farré
Isaac Almendros
Josep M. Montserrat
Nicole E. Benfante
A. Ari Hakimi
Anders J. Skanderup
Paul Russo
Antonio Alcaraz
Karim A. Touijer
Publikationsdatum
23.04.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
World Journal of Urology / Ausgabe 1/2017
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-016-1830-6

Weitere Artikel der Ausgabe 1/2017

World Journal of Urology 1/2017 Zur Ausgabe

Update Urologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.