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  • Original Article
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Clinical Research

Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort

Abstract

BACKGROUND:

Metabolic syndrome (MetS) has been hypothesized to be associated with cancer, including prostate cancer (PCa), but the relationship is not well characterized. We analyze the relationship between MetS features and localized PCa recurrence after treatment.

METHODS:

Men having primary treatment for localized PCa were included from a multi-site regional veteran network. Recurrence was defined as nadir PSA +2 ng ml−1 (radiation) or PSA0.2 ng ml−1 (prostatectomy). MetS was based on consensus professional society guidelines from the American Heart Association and International Diabetes Federation (three of: hypertension >130/85 mm Hg, fasting blood glucose 100 mg dl−1, waist circumference >102 cm, high-density lipoprotein <40 mg dl−1, triglycerides 150 mg dl−1). Closely related abnormality in low-density lipoprotein (LDL; >130 mg dl−1) was also examined. Analysis of PCa recurrence risk included multivariable Cox proportional hazards regression with propensity adjustment.

RESULTS:

Of the 1706 eligible men, 279 experienced recurrence over a median follow-up period of 41 months (range 1–120 months). Adjustment variables associated with PCa recurrence included: index PSA, Gleason, and tumor stage. Independent variables of interest associated with PCa recurrence were hyperglycemia and elevated LDL. Elevated LDL was associated with PCa recurrence (multivariable hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.03, 1.74; propensity adjusted HR 1.33, 95% CI 1.03, 1.72). There was also an association between impaired fasting glucose and PCa recurrence in (multivariable HR 1.54, 95% CI 1.10, 2.15; propensity adjusted HR 1.41, 95% CI 1.01, 1.95). MetS was not associated with PCa recurrence (multivariable: HR 0.96, 95% CI 0.61, 1.50; propensity adjusted HR 1.04, 95% CI 0.67, 1.62).

CONCLUSIONS:

PCa recurrence is not associated with MetS but is associated with elevated LDL and impaired fasting glucose. If confirmed, these data may help provide modifiable targets in preventing recurrence of PCa.

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References

  1. Howlader N, Noone A, Krapcho M, Garshella J, Neyman N, Altekruse SF et al. SEER Cancer Statistics Review, 1975-2010 (With Additional Information from Online Fact Sheets for 2014). National Cancer Institute: Bethesda, MD, USA, 2013.

    Google Scholar 

  2. Nguyen CT, Kattan MW . Formalized prediction of clinically significant prostate cancer: is it possible? Asian J Androl 2012; 14: 349–354.

    Article  Google Scholar 

  3. Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203–213.

    Article  CAS  Google Scholar 

  4. 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 

  5. Swindle PW, Kattan MW, Scardino PT . Markers and meaning of primary treatment failure. Urol Clin N Am 2003; 30: 377–401.

    Article  Google Scholar 

  6. 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 

  7. Brawley OW . Prostate cancer epidemiology in the United States. World J Urol 2012; 30: 195–200.

    Article  Google Scholar 

  8. Asmar R, Beebe-Dimmer JL, Korgavkar K, Keele GR, Cooney KA . Hypertension, obesity and prostate cancer biochemical recurrence after radical prostatectomy. Prostate Cancer Prostatic Dis 2013; 16: 62–66.

    Article  CAS  Google Scholar 

  9. Komaru A, Kamiya N, Suzuki H, Endo T, Takano M, Yano M et al. Implications of body mass index in Japanese patients with prostate cancer who had undergone radical prostatectomy. Jpn J Clin Oncol 2010; 40: 353–359.

    Article  Google Scholar 

  10. 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 2011; 2011: 245642.

    Article  Google Scholar 

  11. Mandair D, Rossi RE, Pericleous M, Whyand T, Caplin ME . Prostate cancer and the influence of dietary factors and supplements: a systematic review. Nutr Metab 2014; 11: 30.

    Article  Google Scholar 

  12. Ahn J, Albanes D, Peters U, Schatzkin A, Lim U, Freedman M et al. Dairy products, calcium intake, and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev 2007; 16: 2623–2630.

    Article  CAS  Google Scholar 

  13. Tseng M, Giri V, Watkins-Bruner D, Giovannucci E . Dairy intake and 1,25-dihydroxyvitamin D levels in men at high risk for prostate cancer. Cancer Causes Control 2009; 20: 1947–1954.

    Article  Google Scholar 

  14. Bhindi B, Locke J, Alibhai SM, Kulkarni GS, Margel DS, Hamilton RJ et al. Dissecting the association between metabolic syndrome and prostate cancer risk: analysis of a large clinical cohort. Eur Urol 2014; 67: 64–70.

    Article  Google Scholar 

  15. Morote J, Ropero J, Planas J, Bastaros JM, Delgado G, Placer J et al. Metabolic syndrome increases the risk of aggressive prostate cancer detection. BJU Int 2013; 111: 1031–1036.

    Article  CAS  Google Scholar 

  16. Ozbek E, Otunctemur A, Dursun M, Sahin S, Besiroglu H, Koklu I et al. The metabolic syndrome is associated with more aggressive prostate cancer. Asian Pac J Cancer Prev 2014; 15: 4029–4032.

    Article  Google Scholar 

  17. Sourbeer KN, Howard LE, Andriole GL, Moreira DM, Castro-Santamaria R, Freedland SJ et al. Metabolic syndrome-like components and prostate cancer risk: results from the REDUCE Study. BJU Int 2014; (E-pub ahead of print).

  18. Lund Haheim L, 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  CAS  Google Scholar 

  19. Eckel RH, Grundy SM, Zimmet PZ . The metabolic syndrome. Lancet 2005; 365: 1415–1428.

    Article  CAS  Google Scholar 

  20. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr., Clark LT, Hunninghake DB et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110: 227–239.

    Article  Google Scholar 

  21. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640–1645.

    Article  CAS  Google Scholar 

  22. Zeliadt SB, Sekaran NK, Hu EY, Slatore CC, Au DH, Backhus L et al. Comparison of demographic characteristics, surgical resection patterns, and survival outcomes for veterans and nonveterans with non-small cell lung cancer in the Pacific Northwest. J Thorac Oncol 2011; 6: 1726–1732.

    Article  Google Scholar 

  23. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129 (Suppl 2): S1–S45.

    Article  Google Scholar 

  24. Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D'Amico AV, Dmochowski RR et al. Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol 2007; 177: 540–545.

    Article  CAS  Google Scholar 

  25. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 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 

  26. Castillejos-Molina R, Rodriguez-Covarrubias F, Sotomayor M, Gomez-Alvarado MO, Villalobos-Gollas M, Gabilondo F et al. Impact of metabolic syndrome on biochemical recurrence of prostate cancer after radical prostatectomy. Urol Int 2011; 87: 270–275.

    Article  Google Scholar 

  27. 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 

  28. Shiota M, Yokomizo A, Takeuchi A, Imada K, Kiyoshima K, Inokuchi J et al. The feature of metabolic syndrome is a risk factor for biochemical recurrence after radical prostatectomy. J Surg Oncol 2014; 110: 476–481.

    Article  Google Scholar 

  29. Xiang YZ, Xiong H, Cui ZL, Jiang SB, Xia QH, Zhao Y et al. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence. J Exp Clin Cancer Res 2013; 32: 9.

    Article  Google Scholar 

  30. Mondul AM, Clipp SL, Helzlsouer KJ, Platz EA . Association between plasma total cholesterol concentration and incident prostate cancer in the CLUE II cohort. Cancer Causes Control 2010; 21: 61–68.

    Article  Google Scholar 

  31. Platz EA, Clinton SK, Giovannucci E . Association between plasma cholesterol and prostate cancer in the PSA era. Int J Cancer 2008; 123: 1693–1698.

    Article  CAS  Google Scholar 

  32. Wright JL, Plymate SR, Porter MP, Gore JL, Lin DW, Hu E et al. Hyperglycemia and prostate cancer recurrence in men treated for localized prostate cancer. Prostate Cancer Prostatic Dis 2013; 16: 204–208.

    Article  CAS  Google Scholar 

  33. Ogden CL, Carroll MD, Kit BK, Flegal KM . Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014; 311: 806–814.

    Article  CAS  Google Scholar 

  34. Ford ES, Li C, Zhao G . Prevalence and correlates of metabolic syndrome based on a harmonious definition among adults in the US. J Diabetes 2010; 2: 180–193.

    Article  Google Scholar 

  35. Gutt R, Tonlaar N, Kunnavakkam R, Karrison T, Weichselbaum RR, Liauw SL . Statin use and risk of prostate cancer recurrence in men treated with radiation therapy. J Clin Oncol 2010; 28: 2653–2659.

    Article  CAS  Google Scholar 

  36. Scosyrev E, Tobis S, Donsky H, Wu G, Joseph J, Rashid H et al. Statin use and the risk of biochemical recurrence of prostate cancer after definitive local therapy: a meta-analysis of eight cohort studies. BJU Int 2013; 111 (Pt B): E71–E77.

    Article  Google Scholar 

  37. Park C, Lee I, Kang WK . Lovastatin-induced E2F-1 modulation and its effect on prostate cancer cell death. Carcinogenesis 2001; 22: 1727–1731.

    Article  CAS  Google Scholar 

  38. Brown M, Hart C, Tawadros T, Ramani V, Sangar V, Lau M et al. The differential effects of statins on the metastatic behaviour of prostate cancer. Br J Cancer 2012; 106: 1689–1696.

    Article  CAS  Google Scholar 

  39. Murtola TJ, Syvala H, Pennanen P, Blauer M, Solakivi T, Ylikomi T et al. Comparative effects of high and low-dose simvastatin on prostate epithelial cells: the role of LDL. Eur J Pharmacol 2011; 673: 96–100.

    Article  CAS  Google Scholar 

  40. Monroe AK, Dobs AS . The effect of androgens on lipids. Curr Opin Endocrinol Diabetes Obes 2013; 20: 132–139.

    Article  CAS  Google Scholar 

  41. Fenton MA, Shuster TD, Fertig AM, Taplin ME, Kolvenbag G, Bubley GJ et al. Functional characterization of mutant androgen receptors from androgen-independent prostate cancer. Clin Cancer Res 1997; 3: 1383–1388.

    CAS  PubMed  Google Scholar 

  42. Labrie F . Adrenal androgens and intracrinology. Semin Reprod Med 2004; 22: 299–309.

    Article  CAS  Google Scholar 

  43. Veldscholte J, Ris-Stalpers C, Kuiper GG, Jenster G, Berrevoets C, Claassen E et al. A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commun 1990; 173: 534–540.

    Article  CAS  Google Scholar 

  44. Cai C, Chen S, Ng P, Bubley GJ, Nelson PS, Mostaghel EA et al. Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors. Cancer Res 2011; 71: 6503–6513.

    Article  CAS  Google Scholar 

  45. Mostaghel EA, Solomon KR, Pelton K, Freeman MR, Montgomery RB . Impact of circulating cholesterol levels on growth and intratumoral androgen concentration of prostate tumors. PLoS One 2012; 7: e30062.

    Article  CAS  Google Scholar 

  46. Cao Y, Lindstrom S, Schumacher F, Stevens VL, Albanes D, Berndt S et al. Insulin-like growth factor pathway genetic polymorphisms, circulating IGF1 and IGFBP3, and prostate cancer survival. J Natl Cancer Inst 2014; 106: dju085.

    Article  Google Scholar 

  47. Cheng I, Stram DO, Penney KL, Pike M, Le Marchand L, Kolonel LN et al. Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort. J Natl Cancer Inst 2006; 98: 123–134.

    Article  CAS  Google Scholar 

  48. Giorgi EE, Stram DO, Taverna D, Turner SD, Schumacher F, Haiman CA et al. Fine-mapping IGF1 and prostate cancer risk in African Americans: the Multiethnic Cohort Study. Cancer Epidemiol Biomarkers Prev 2014; 23: 1928–1932.

    Article  CAS  Google Scholar 

  49. Llaverias G, Danilo C, Wang Y, Witkiewicz AK, Daumer K, Lisanti MP et al. A Western-type diet accelerates tumor progression in an autochthonous mouse model of prostate cancer. Am J Pathol 2010; 177: 3180–3191.

    Article  CAS  Google Scholar 

  50. Moschos SJ, Mantzoros CS . The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 2002; 63: 317–332.

    Article  CAS  Google Scholar 

  51. Yu H, Yin L, Jiang X, Sun X, Wu J, Tian H et al. Effect of metformin on cancer risk and treatment outcome of prostate cancer: a meta-analysis of epidemiological observational studies. PLoS One 2014; 9: e116327.

    Article  Google Scholar 

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Acknowledgements

This work was supported by an NIH Grant: P50CA097186 from the National Cancer Institute, with additional support and resources from the Fred Hutchinson Cancer Research Center and VA Puget Sound Health Care system.

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Correspondence to L C Macleod.

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Macleod, L., Chery, L., Hu, E. et al. Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort. Prostate Cancer Prostatic Dis 18, 190–195 (2015). https://doi.org/10.1038/pcan.2015.12

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