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Clinical Research

Hypertension, obesity and prostate cancer biochemical recurrence after radical prostatectomy

Abstract

Background:

The metabolic syndrome (MetS) comprises a constellation of risk factors associated with an increased risk for cardiovascular disease. Components of MetS have emerged as putative risk factors for prostate carcinoma. In this study, we examine the association between three features of the MetS (obesity, hypertension and diabetes) and the risk of biochemical recurrence (BCR) after radical prostatectomy (RP).

Methods:

We examined data from 1428 men in the University of Michigan Prostate Cancer Data Bank who elected to have RP as their primary treatment. We calculated body mass index from patients’ weight and height measured at the time of prostate cancer diagnosis. We used the University of Michigan’s Electronic Medical Record Search Engine to identify subjects with hypertension and/or diabetes before their prostate cancer diagnosis.

Results:

Of 1428 men who underwent RP, 107 (8%) subsequently developed BCR with a median length of follow-up post-surgery of 3.6 years. Obesity and hypertension were each associated with an increased risk of BCR (adjusted hazard ratio (aHR)=1.37; 95% CI 0.92–2.09 and aHR=1.51, 95% CI 1.01–2.26), whereas no association was observed between diabetes and BCR (aHR=0.73; 95% CI 0.40–1.33).

Conclusions:

Obesity and hypertension were each associated with an increased risk for BCR of prostate cancer after RP, independent of age at diagnosis and tumor pathological features. Given the increasing rates of obesity, hypertension and prostate cancer, a better understanding of the relationship between these entities is of significant public health importance. Elucidation of the involved pathogenic mechanisms will be needed to establish causality.

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References

  1. Reaven GM . Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med 1993; 44: 121–131.

    Article  CAS  Google Scholar 

  2. Mozumdar A, Liguori G . Persistent increase of prevalence of metabolic syndrome among U.S. adults: NHANES III to NHANES 1999-2006. Diabetes Care 2011; 34: 216–219.

    Article  Google Scholar 

  3. Day C . Metabolic syndrome, or what you will: definitions and epidemiology. Diab Vasc Dis Res 2007; 4: 32–38.

    Article  Google Scholar 

  4. Cleeman JI . Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001; 285: 2486–2497.

    Article  Google Scholar 

  5. Akintunde AA, Ayodele OE, Akinwusi PO, Opadijo GO . Metabolic syndrome: comparison of occurrence using three definitions in hypertensive patients. Clinl Med Res 2011; 9: 26–31.

    Article  Google Scholar 

  6. Laukkanen JA, Laaksonen DE, Niskanen L, Pukkala E, Hakkarainen A, Salonen JT . Metabolic syndrome and the risk of prostate cancer in Finnish men: a population-based study. Cancer Epidemiol Biomarkers Prev 2004; 13: 1646–1650.

    CAS  PubMed  Google Scholar 

  7. Lund HL, Wisloff TF, Holme I, Nafstad P . Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian men followed for 27 years. Am J Epidemiol 2006; 164: 769–774.

    Article  Google Scholar 

  8. Beebe-Dimmer JL, Dunn RL, Sarma AV, Montie JE, Cooney KA . Features of the metabolic syndrome and prostate cancer in African-American men. Cancer 2007; 109: 875–881.

    Article  Google Scholar 

  9. De Nunzio C, Freedland SJ, Miano R, Trucchi A, Cantiani A, Carluccini A et al. Metabolic syndrome is associated with high grade gleason score when prostate cancer is diagnosed on biopsy. Prostate 2011; 71: 1492–1498.

    PubMed  Google Scholar 

  10. Tuohimaa P, Tenkanen L, Syvala H, Lumme S, Hakulinen T, Dillner J et al. Interaction of factors related to the metabolic syndrome and vitamin D on risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2007; 16: 302–307.

    Article  CAS  Google Scholar 

  11. Post JM, Beebe-Dimmer JL, Morgenstern H, Neslund-Dudas C, Bock CH, Nock N et al. The metabolic syndrome and biochemical recurrence following radical prostatectomy. Prostate Cancer 2012; 2011: 245642.

    Google Scholar 

  12. Bray GA . The underlying basis for obesity: relationship to cancer. J Nutr 2002; 132: 3451s–3455s.

    Article  CAS  Google Scholar 

  13. Freedland SJ, Aronson WJ, Kane CJ, Presti JC, Amling CL, Elashoff D et al. Impact of obesity on biochemical control after radical prostatectomy for clinically localized prostate cancer: a report by the Shared Equal Access Regional Cancer Hospital database study group. J Clin Oncol 2004; 22: 446–453.

    Article  Google Scholar 

  14. Freedland SJ, Platz EA . Obesity and prostate cancer: making sense out of apparently conflicting data. Epidemiol Rev 2007; 29: 88–97.

    Article  Google Scholar 

  15. Montgomery JS, Gayed BA, Hollenbeck BK, Daignault S, Sanda MG, Montie JE et al. Obesity adversely affects health related quality of life before and after radical retropubic prostatectomy. J Urol 2006; 176: 257–261.

    Article  Google Scholar 

  16. Partin AW, Oesterling JE . The clinical usefulness of prostate specific antigen: update 1994. J Urol 1994; 152: 1358–1368.

    Article  CAS  Google Scholar 

  17. Cronin AM, Godoy G, Vickers AJ . Definition of biochemical recurrence after radical prostatectomy does not substantially impact prognostic factor estimates. J Urol 2010; 183: 984–989.

    Article  Google Scholar 

  18. Hanauer DA . EMERSE: The Electronic Medical Record Search Engine. American Medical Informatics Association Annual Symposium Proceedings 2006,, 1189.

  19. Siegel R, Ward E, Brawley O, Jemal A . Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61: 212–236.

    Article  Google Scholar 

  20. Etzioni R, Penson DF, Legler JM, di Tommaso D, Boer R, Gann PH et al. Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends. J Natl Cancer Inst 2002; 94: 981–990.

    Article  Google Scholar 

  21. Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO, Bratell S et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005; 352: 1977–1984.

    Article  CAS  Google Scholar 

  22. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC . Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999; 281: 1591–1597.

    Article  CAS  Google Scholar 

  23. Simmons MN, Stephenson AJ, Klein EA . Natural history of biochemical recurrence after radical prostatectomy: risk assessment for secondary therapy. Eur Urol 2007; 51: 1175–1184.

    Article  Google Scholar 

  24. Hsing AW, Sakoda LC, Chua S . Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr 2007; 86: s843–s857.

    Article  Google Scholar 

  25. Freedland SJ, Terris MK, Presti JC, Amling CL, Kane CJ, Trock B et al. Obesity and biochemical outcome following radical prostatectomy for organ confined disease with negative surgical margins. J Urol 2004; 172: 520–524.

    Article  Google Scholar 

  26. Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV et al. Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev 2007; 16: 63–69.

    Article  Google Scholar 

  27. Okasha M, McCarron P, McEwen J, Smith GD . Body mass index in young adulthood and cancer mortality: a retrospective cohort study. J Epidemiol Community Health 2002; 56: 780–784.

    Article  CAS  Google Scholar 

  28. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ . Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348: 1625–1638.

    Article  Google Scholar 

  29. Wright ME, Chang SC, Schatzkin A, Albanes D, Kipnis V, Mouw T et al. Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality. Cancer 2007; 109: 675–684.

    Article  Google Scholar 

  30. Beebe-Dimmer JL, Faerber GJ, Morgenstern H, Werny D, Wojno K, Halstead-Nussloch B et al. Body composition and serum prostate-specific antigen: review and findings from Flint Men’s Health Study. Urology 2008; 71: 554–560.

    Article  Google Scholar 

  31. Friedman GD . Blood pressure and heart rate: no evidence for a positive association with prostate cancer. Ann Epidemiol 1997; 7: 486–489.

    Article  CAS  Google Scholar 

  32. Fitzpatrick AL, Daling JR, Furberg CD, Kronmal RA, Weissfeld JL . Hypertension, heart rate, use of antihypertensives, and incident prostate cancer. Ann Epidemiol 2001; 11: 534–542.

    Article  CAS  Google Scholar 

  33. Hammarsten J, Högstedt B . Clinical haemodynamic, anthropometric, metabolic and insulin profile of men with high-stage and high-grade clinical prostate cancer. Blood Press 2004; 13: 47–55.

    Article  CAS  Google Scholar 

  34. Bonovas S, Filioussi K, Tsantes A . Diabetes mellitus and risk of prostate cancer: a meta-analysis. Diabetologia 2004; 47: 1071–1078.

    Article  CAS  Google Scholar 

  35. Rodriguez C, Patel AV, Mondul AM, Jacobs EJ, Thun MJ, Calle EE . Diabetes and risk of prostate cancer in a prospective cohort of US men. Am J Epidemiol 2005; 161: 147–152.

    Article  Google Scholar 

  36. Chokkalingam AP, Pollak M, Fillmore CM, Gao YT, Stanczyk FZ, Deng J et al. Insulin-like growth factors and prostate cancer: a population-based case-control study in China. Cancer Epidemiol Biomarkers Prev 2001; 10: 421–427.

    CAS  PubMed  Google Scholar 

  37. Kaaks R, Lukanova A, Rinaldi S, Biessy C, Söderberg S, Olsson T . Interrelationships between plasma testosterone, SHBG, IGF-1, insulin and leptin in prostate cancer cases and controls. Eur J Cancer Prev 2003; 12: 309–315.

    Article  CAS  Google Scholar 

  38. Nelson WG, De Marzo AM, DeWeese TL, Isaacs WB . The role of inflammation in the pathogenesis of prostate cancer. J Urol 2004; 172: S6–S11.

    Article  CAS  Google Scholar 

  39. Marchesi C, Ebrahimian T, Angulo O, Paradis P, Schiffrin EL . Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome. Hypertension 2009; 54: 1384–1392.

    Article  CAS  Google Scholar 

  40. Touyz RM . Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension 2004; 44: 248–252.

    Article  CAS  Google Scholar 

  41. Saglam K, Aydur E, Yilmaz M, Göktaş S . Leptin influences cellular differentiation and progression in prostate cancer. J Urol 2003; 169: 1308–1311.

    Article  CAS  Google Scholar 

  42. Shoelson SE, Lee J, Goldfine AB . Inflammation and insulin resistance. J Clin Invest 2006; 116: 1793–1801.

    Article  CAS  Google Scholar 

  43. Ford ES, Giles WH, Dietz WH . Prevalence of metabolic syndrome among U.S. adults:findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287: 356–359.

    Article  Google Scholar 

  44. Klabunde CN, Reeve BB, Harlan LC, Davis WW, Potosky AL . Do patients consistently report comorbid conditions over time?: results from the prostate cancer outcomes study. Med Care 2005; 43: 391–400.

    Article  Google Scholar 

  45. Smith SC, Clark LT, Cooper RS, Daniels SR, Kumanyika SK, Ofili E et al. Discovering the full spectrum of cardiovascular disease: Minority Health Summit 2003: report of the Obesity, Metabolic Syndrome, and Hypertension Writing Group. Circulation 2005; 111: e134–e139.

    PubMed  Google Scholar 

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Acknowledgements

We thank Dr David Hanaeur for assistance with use of EMERSE; and Drs David Wood, John Wei and Mr Michael Coehlo for access and guidance on use of the Radical Prostatectomy Data Bank. Sources of support/funding: NIH P50-CA69568, University of Michigan, Departments of Internal Medicine and Urology, UMCCC.

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Correspondence to R Asmar.

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Asmar, R., Beebe-Dimmer, J., Korgavkar, K. et al. Hypertension, obesity and prostate cancer biochemical recurrence after radical prostatectomy. Prostate Cancer Prostatic Dis 16, 62–66 (2013). https://doi.org/10.1038/pcan.2012.32

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  • DOI: https://doi.org/10.1038/pcan.2012.32

Keywords

  • diabetes
  • hypertension
  • BMI
  • obesity
  • insulin resistance

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