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Metabolic syndrome is associated with aggressive prostate cancer regardless of race

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Abstract

Purpose

Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We investigated MS and PC diagnosis in black and white men undergoing prostate biopsy in an equal access healthcare system. We hypothesized MS would be linked with aggressive PC, regardless of race.

Methods

Among men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, medical record data abstraction of diagnosis or treatment for hypertension (≥ 130/85 mmHg), dyslipidemia (HDL < 40 mg/dL), hypertriglyceridemia (≥ 150 mg/dL), diabetes, hyperglycemia (fasting glucose ≥ 100 ml/dL), and central obesity (waist circumference ≥ 40 inches) were done. Biopsy grade group (GG) was categorized as low (GG1) or high (GG2-5). Multinomial logistic regression was used to examine MS (3–5 components) vs. no MS (0–2 components) and diagnosis of high grade and low grade vs. no PC, adjusting for potential confounders. Interactions between race and MS were also tested.

Results

Of 1,051 men (57% black), 532 (51%) had MS. Men with MS were older, more likely to be non-black, and had a larger prostate volume (all p ≤ 0.011). On multivariable analysis, MS was associated with high-grade PC (OR = 1.73, 95% CI 1.21–2.48, p = 0.003), but not overall PC (OR = 1.17, 95% CI 0.88–1.57, p = 0.29) or low grade (OR = 0.87, 95% CI 0.62–1.21, p = 0.39). Results were similar in black and non-black men (all p-interactions > 0.25).

Conclusion

Our data suggest that metabolic dysregulation advances an aggressive PC diagnosis in both black and non-black men. If confirmed, prevention of MS could reduce the risk of developing aggressive PC, including black men at higher risk of PC mortality.

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Abbreviations

MS:

Metabolic Syndrome

PC:

Prostate Cancer

PSA:

Prostate-Specific Antigen

DRE:

Digital Rectal Exam

TMPRSS2: ERG:

Transmembrane protease, serine 2, erythroblast transformation-specific-related gene

GG:

Gleason Grade

References

  1. Moore JX, Chaudhary N, Akinyemiju T (2017) Metabolic syndrome prevalence by race/ethnicity and sex in the united states, National Health and Nutrition Examination Survey 1988–2012. Prev Chronic Dis 14:E24. https://doi.org/10.5888/pcd14.160287 ((in eng))

    Article  PubMed  PubMed Central  Google Scholar 

  2. Saklayen MG (2018) The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. https://doi.org/10.1007/s11906-018-0812-z ((in eng))

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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) (2001) Jama, 285(19):2486–2497. https://doi.org/10.1001/jama.285.19.2486.

  4. De Pergola G, Silvestris F (2013) Obesity as a major risk factor for cancer. J Obes 2013:291546. https://doi.org/10.1155/2013/291546 ((in eng))

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pothiwala P, Jain SK, Yaturu S (2009) "Metabolic syndrome and cancer. Metab Syndr Relat Disord 7(4):279–288. https://doi.org/10.1089/met.2008.0065 ((in eng))

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jamnagerwalla J et al (2018) Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study. Prostate Cancer Prostatic Dis 21(2):252–259. https://doi.org/10.1038/s41391-017-0030-9 ((in eng))

    Article  CAS  PubMed  Google Scholar 

  7. Gacci M et al (2017) Meta-analysis of metabolic syndrome and prostate cancer. Prostate Cancer Prostatic Dis 20(2):146–155. https://doi.org/10.1038/pcan.2017.1 ((in eng))

    Article  CAS  PubMed  Google Scholar 

  8. Motterle G et al (2021) "Metabolic syndrome and risk of prostate cancer: a systematic review and meta-analysis. Panminerva Med. https://doi.org/10.23736/s0031-0808.21.04507-9 ((in eng))

    Article  PubMed  Google Scholar 

  9. Tande AJ, Platz EA, Folsom AR (2006) The metabolic syndrome is associated with reduced risk of prostate cancer. Am J Epidemiol 164(11):1094–1102

    Article  PubMed  Google Scholar 

  10. Telli O et al (2015) Does metabolic syndrome or its components associate with prostate cancer when diagnosed on biopsy? Ther Adv Med Oncol 7(2):63–67. https://doi.org/10.1177/1758834014560158 ((in eng))

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bhindi B et al (2015) Dissecting the association between metabolic syndrome and prostate cancer risk: analysis of a large clinical cohort. Eur Urol 67(1):64–70. https://doi.org/10.1016/j.eururo.2014.01.040 ((in eng))

    Article  CAS  PubMed  Google Scholar 

  12. Dickerman BA et al (2018) Midlife metabolic factors and prostate cancer risk in later life. Int J Cancer 142(6):1166–1173. https://doi.org/10.1002/ijc.31142 ((in eng))

    Article  CAS  PubMed  Google Scholar 

  13. Zhang JQ, Geng H, Ma M, Nan XY, Sheng BW (2015) Metabolic syndrome components are associated with increased prostate cancer risk. Med Sci Monit 21:2387–2396. https://doi.org/10.12659/msm.893442 ((in eng))

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Beebe-Dimmer JL et al (2009) Racial differences in risk of prostate cancer associated with metabolic syndrome. Urology 74(1):185–190. https://doi.org/10.1016/j.urology.2009.03.013 ((in eng))

    Article  PubMed  Google Scholar 

  15. Beebe-Dimmer JL, Dunn RL, Sarma AV, Montie JE, Cooney KA (2007) Features of the metabolic syndrome and prostate cancer in African-American men. Cancer 109(5):875–881. https://doi.org/10.1002/cncr.22461 ((in eng))

    Article  PubMed  Google Scholar 

  16. Banez LL et al (2007) Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer. JAMA, J Am Med Assoc 298(19):2275–2280 ((in eng))

    Article  Google Scholar 

  17. Freedland SJ et al (2006) Obesity, serum prostate specific antigen and prostate size: implications for prostate cancer detection. J Urol 175(2):500–504

    Article  PubMed  Google Scholar 

  18. Carson AP, Howard G, Burke GL, Shea S, Levitan EB, Muntner P (2011) Ethnic differences in hypertension incidence among middle-aged and older U. S. adults: the multi-ethnic study of atherosclerosis. Hypertension 57(6):1101–1107. https://doi.org/10.1161/hypertensionaha.110.168005 ((in eng))

    Article  CAS  PubMed  Google Scholar 

  19. Kwagyan J et al (2015) Obesity and cardiovascular diseases in a high-risk population: evidence-based approach to chd risk reduction. Ethn Dis 25(2):208–213 ((in eng))

    PubMed  Google Scholar 

  20. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics. CA Cancer J Clin 68(1):7–30. https://doi.org/10.3322/caac.21442 ((in eng))

    Article  PubMed  Google Scholar 

  21. Sourbeer KN et al (2015) Metabolic syndrome-like components and prostate cancer risk: results from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. BJU Int 115(5):736–743. https://doi.org/10.1111/bju.12843 ((in eng))

    Article  CAS  PubMed  Google Scholar 

  22. Gaines AR et al (2014) The association between race and prostate cancer risk on initial biopsy in an equal access, multiethnic cohort. Cancer Causes Control 25(8):1029–1035. https://doi.org/10.1007/s10552-014-0402-6

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mucci LA, Stampfer MJ (2014) Mounting evidence for prediagnostic use of statins in reducing risk of lethal prostate cancer. J Clin Oncol 32(1):1–2. https://doi.org/10.1200/jco.2013.53.2770

    Article  CAS  PubMed  Google Scholar 

  24. Yu H et al (2014) Effect of metformin on cancer risk and treatment outcome of prostate cancer: a meta-analysis of epidemiological observational studies. PLoS ONE. https://doi.org/10.1371/journal.pone.0116327 ((in eng))

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  26. Freedland SJ, Terris MK, Platz EA, Presti JC Jr (2005) Body mass index as a predictor of prostate cancer: development versus detection on biopsy. Urology 66(1):108–113

    Article  PubMed  Google Scholar 

  27. Rhee H, Vela I, Chung E (2016) Metabolic syndrome and prostate cancer: a review of complex interplay amongst various endocrine factors in the pathophysiology and progression of prostate cancer. Horm Cancer 7(2):75–83. https://doi.org/10.1007/s12672-015-0238-x ((in eng))

    Article  CAS  PubMed  Google Scholar 

  28. Sfanos KS, De Marzo AM (2012) Prostate cancer and inflammation: the evidence. Histopathology 60(1):199–215. https://doi.org/10.1111/j.1365-2559.2011.04033.x ((in eng))

    Article  PubMed  PubMed Central  Google Scholar 

  29. Arcidiacono B et al (2012) Insulin resistance and cancer risk: an overview of the pathogenetic mechanisms. Exp Diabetes Res 2012:789174. https://doi.org/10.1155/2012/789174 ((in eng))

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mani RS et al (2016) Inflammation induced oxidative stress mediates gene fusion formation in prostate cancer. Cell Rep 17(10):2620–2631. https://doi.org/10.1016/j.celrep.2016.11.019 ((in eng))

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Demichelis F et al (2007) TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 26(31):4596–4599. https://doi.org/10.1038/sj.onc.1210237 ((in eng))

    Article  CAS  PubMed  Google Scholar 

  32. Pettersson A et al (2013) Modification of the association between obesity and lethal prostate cancer by TMPRSS2:ERG. J Natl Cancer Inst 105(24):1881–1890. https://doi.org/10.1093/jnci/djt332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhou CK et al (2017) TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences. Am J Epidemiol 186(12):1352–1361. https://doi.org/10.1093/aje/kwx235 ((in eng))

    Article  PubMed  PubMed Central  Google Scholar 

  34. Morote J et al (2014) Role of Serum Cholesterol and Statin Use in the Risk of Prostate Cancer Detection and Tumor Aggressiveness. Int J Mol Sci 15(8):13615–13623. https://doi.org/10.3390/ijms150813615 ((in eng))

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fujita K, Hayashi T, Matsushita M, Uemura M, Nonomura N (2019) Obesity, Inflammation, and Prostate Cancer. J Clin Med. https://doi.org/10.3390/jcm8020201 ((in eng))

    Article  PubMed  PubMed Central  Google Scholar 

  36. Mostaghel EA, Solomon KR, Pelton K, Freeman MR, Montgomery RB (2012) Impact of circulating cholesterol levels on growth and intratumoral androgen concentration of prostate tumors. PLoS ONE 7(1):e30062. https://doi.org/10.1371/journal.pone.0030062 ((in eng))

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kelkar S et al (2021) Diabetes and Prostate cancer outcomes in obese and nonobese men after radical prostatectomy. JNCI Cancer Spectr 5(3):pkab023. https://doi.org/10.1093/jncics/pkab023 ((in eng))

    Article  PubMed  PubMed Central  Google Scholar 

  38. Carroll PH, Mohler JL (2018) NCCN guidelines updates: prostate cancer and prostate cancer early detection. J Natl Compr Canc Netw 16(5s):620–623. https://doi.org/10.6004/jnccn.2018.0036 ((in eng))

    Article  PubMed  Google Scholar 

  39. Schulman AA et al (2017) Validation of the 2015 prostate cancer grade groups for predicting long-term oncologic outcomes in a shared equal-access health system. Cancer 123(21):4122–4129. https://doi.org/10.1002/cncr.30844 ((in eng))

    Article  PubMed  Google Scholar 

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Funding

LEADS Support; National Institute of General Medical Sciences, R25 GM116740 (LGR). Research Scholar Grant, RSG-18–018-01—CPHPS, from the American Cancer Society. (AV).

Author information

Author notes

  1. Jay H. Fowke and Stephen J. Freedland have contributed equally as co-senior authors.

Authors and Affiliations

  1. Urology Section, Surgery Department, Veterans Administration Caribbean Healthcare System, San Juan, Puerto Rico

    Lourdes Guerrios-Rivera

  2. University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico

    Lourdes Guerrios-Rivera

  3. Duke Cancer Institute, Duke University School of Medicine, Duke, USA

    Lauren E. Howard

  4. Veterans Affairs Medical Center Durham, Urology Section, 508 Fulton St, Durham, NC, 27705, USA

    Lauren E. Howard, Emily K. Wiggins, Tyler R. Erickson, Jaruda Ithisuphalap & Stephen J. Freedland

  5. North Carolina State Department of Biology and Cancer Research Program, 2200 Hillsborough, Raleigh, NC, 27695, USA

    Cathrine Hoyo

  6. Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 1801 Fayetteville Street, Durham, NC, USA

    Delores J. Grant

  7. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Jay H. Fowke

  8. Division of Epidemiology, Department of Preventive Medicine, University of Tennessee Health Science Center, Doctor’s Office Building, 66 N. Pauline Street, Suite 600, Memphis, TN, 38163, USA

    Jay H. Fowke

  9. Dept of Epidemiology, UCI School of Medicine, University of California, 1001 Health Sciences Rd, Irvine, CA, 92617, USA

    Alexis R. Freedland

  10. Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8635 West 3rd Street Suite 1070W, Los Angeles, CA, 90048, USA

    Adriana C. Vidal & Stephen J. Freedland

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  1. Lourdes Guerrios-Rivera
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Contributions

Included all the authors associated to this manuscript: LGR, MD, MSc; LEH MS; EKW MPH; CH PhD; DJG PhD, MPH; TRE MS; JI MS; ARF MS, PhD (c); ACV, PhD; JHF PhD; and SJF MD. Conceptualization: LG-R, LEH, JHF, and SJF; Data curation: LEH, TRE, JI, EKW, CH, DJG, and SJF; Formal analysis: LEH, TRE, JI, and SJF; Investigation: LG-R, LEH, EKW, CH, DJG, ARF, ACV, JHF, and SJF; Methodology: LG-R, LEH, EKW, CH, DJG, TRE, JI, ARF, ACV, JHF, and SJF, Project administration: LG-R, LEH, EKW, and SJF; Writing of the original draft: LG, LH, JHF, and SF; Writing, reviewing, & editing of the manuscript: LG-R, LEH, EKW, CH, DJG, TRE, JI, ARF, ACV, JHF, and SJF.

Corresponding author

Correspondence to Lourdes Guerrios-Rivera.

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The authors have no financial or proprietary interests in any material discussed in this article. There are no direct or indirect commercial financial incentives associated with publishing the article. No funding agreement limits my ability to complete and publish this research/study.

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The study was approved by Durham VA Medical Center Institutional Review Board, reference number #1141.

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Informed consent was obtained from all individual participants included in the study.

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Guerrios-Rivera, L., Howard, L.E., Wiggins, E.K. et al. Metabolic syndrome is associated with aggressive prostate cancer regardless of race. Cancer Causes Control 34, 213–221 (2023). https://doi.org/10.1007/s10552-022-01649-9

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  • DOI: https://doi.org/10.1007/s10552-022-01649-9

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