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Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study

Abstract

Background

Epidemiologic evidence for a serum cholesterol-prostate cancer link is mixed. Prostate-specific antigen (PSA) is positively correlated with cholesterol, potentially increasing PSA-driven biopsy recommendations in men with high cholesterol, though biopsy compliance may be lower in men with comorbid conditions. These potential biases may affect PSA-driven biopsy rates and subsequent prostate cancer detection in men with high serum cholesterol. Our objective was to test the association between serum cholesterol and prostate cancer risk in men receiving PSA independent, study-mandated prostate biopsies.

Methods

We conducted a post hoc analysis of data from 4974 non-statin users in REDUCE, a randomized trial in men with elevated PSA and a negative baseline biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies. Associations between baseline serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and prostate cancer risk, overall and by Gleason grade (<7 vs. ≥7), were examined using multivariable logistic regression.

Results

High total serum cholesterol was associated with an increased risk of high-grade prostate cancer diagnosis (OR per 10 mg/dL 1.05; 95% CI 1.00–1.09; p = 0.048), but cholesterol was unrelated to either overall or low-grade prostate cancer risk (p-values >0.185). There was no association between serum LDL and overall, low- or high-grade prostate cancer risk (p-values >0.137). In contrast, elevated serum HDL was associated with increased risk of both overall (OR per 10 mg/dL 1.08; 95% CI 1.01–1.16; p = 0.033) and high-grade prostate cancer (OR per 10 mg/dL 1.14; 95% CI 1.01–1.28; p = 0.034).

Conclusions

In REDUCE, where all men received PSA independent, trial-mandated biopsies thus ensuring complete prostate cancer ascertainment, high total serum cholesterol and high HDL were associated with increased risk of high-grade prostate cancer, supporting a cholesterol-prostate cancer link.

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References

  1. 1.

    Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4:579–91.

    CAS  Article  Google Scholar 

  2. 2.

    Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013;63:800–9.

    CAS  Article  Google Scholar 

  3. 3.

    Ishikawa-Takata K, Ohta T, Moritaki K, Gotou T, Inoue S. Obesity, weight change and risks for hypertension, diabetes and hypercholesterolemia in Japanese men. Eur J Clin Nutr. 2002;56:601–7.

    CAS  Article  Google Scholar 

  4. 4.

    Pelton K, Freeman MR, Solomon KR. Cholesterol and prostate cancer. Curr Opin Pharmacol. 2012;12:751–9.

    CAS  Article  Google Scholar 

  5. 5.

    Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest. 2005;115: 959–68.

    CAS  Article  Google Scholar 

  6. 6.

    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;177:3180–91.

    CAS  Article  Google Scholar 

  7. 7.

    Solomon KR, Pelton K, Boucher K, Joo J, Tully C, Zurakowski D, et al. Ezetimibe is an inhibitor of tumor angiogenesis. Am J Pathol. 2009;174:1017–26.

    CAS  Article  Google Scholar 

  8. 8.

    Mondul AM, Weinstein SJ, Virtamo J, Albanes D. Serum total and HDL cholesterol and risk of prostate cancer. Cancer Causes Control. 2011;22:1545–52.

    Article  Google Scholar 

  9. 9.

    Platz EA, Till C, Goodman PJ, Parnes HL, Figg WD, Albanes D, et al. Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomark Prev. 2009;18:2807–13.

    CAS  Article  Google Scholar 

  10. 10.

    Heir T, Falk RS, Robsahm TE, Sandvik L, Erikssen J, Tretli S. Cholesterol and prostate cancer risk: a long-term prospective cohort study. BMC Cancer. 2016;16:643.

    Article  Google Scholar 

  11. 11.

    YuPeng L, YuXue Z, PengFei L, Cheng C, YaShuang Z, DaPeng L, et al. Cholesterol Levels in Blood and the Risk of Prostate Cancer: A Meta-analysis of 14 Prospective Studies. Cancer Epidemiol, Biomark Prev. 2015;24:1086–93.

    Article  Google Scholar 

  12. 12.

    Zapata D, Howard LE, Allott EH, Hamilton RJ, Goldberg K, Freedland SJ. Is PSA related to serum cholesterol and does the relationship differ between black and white men? Prostate. 2015;75:1877–85.

    CAS  Article  Google Scholar 

  13. 13.

    Hamilton RJ, Goldberg KC, Platz EA, Freedland SJ. The influence of statin medications on prostate-specific antigen levels. J Natl Cancer Inst. 2008;100:1511–8.

    CAS  Article  Google Scholar 

  14. 14.

    Fischer S, Sun S, Howard LE, Moreira DM, Castro-Santamaria R, Andriole GL, et al. Baseline subject characteristics predictive of compliance with study-mandated prostate biopsy in men at risk of prostate cancer: results from REDUCE. Prostate Cancer Prostatic Dis. 2016;19:202–8.

    CAS  Article  Google Scholar 

  15. 15.

    Tangen CM, Goodman PJ, Till C, Schenk JM, Lucia MS, Thompson IM Jr.. Biases in recommendations for and acceptance of prostate biopsy significantly affect assessment of prostate cancer risk factors: results from two large randomized clinical trials. J Clin Oncol. 2016;34:4338–44.

    CAS  Article  Google Scholar 

  16. 16.

    Andriole G, Bostwick D, Brawley O, Gomella L, Marberger M, Tindall D, et al. Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial. J Urol. 2004;172:1314–7. (4 Pt 1)

    CAS  Article  Google Scholar 

  17. 17.

    Freedland SJ, Hamilton RJ, Gerber L, Banez LL, Moreira DM, Andriole GL, et al. Statin use and risk of prostate cancer and high-grade prostate cancer: results from the REDUCE study. Prostate Cancer Prostatic Dis. 2013;16:254–9.

    CAS  Article  Google Scholar 

  18. 18.

    National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. 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) final report. Circulation. 2002;106:3143–421.

    Article  Google Scholar 

  19. 19.

    de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.

    Article  Google Scholar 

  20. 20.

    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.

    CAS  Article  Google Scholar 

  21. 21.

    Farwell WR, D’Avolio LW, Scranton RE, Lawler EV, Gaziano JM. Statins and prostate cancer diagnosis and grade in a veterans population. J Natl Cancer Inst. 2011;103:885–92.

    CAS  Article  Google Scholar 

  22. 22.

    Van Hemelrijck M, Walldius G, Jungner I, Hammar N, Garmo H, Binda E, et al. Low levels of apolipoprotein A-I and HDL are associated with risk of prostate cancer in the Swedish AMORIS study. Cancer Causes Control. 2011;22:1011–9.

    Article  Google Scholar 

  23. 23.

    Toth PP. High-density lipoprotein as a therapeutic target: clinical evidence and treatment strategies. Am J Cardiol. 2005;96:50K–58K. Discussion 34K–35K.

    CAS  Article  Google Scholar 

  24. 24.

    Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012;380:572–80.

    CAS  Article  Google Scholar 

  25. 25.

    Keene D, Price C, Shun-Shin MJ, Francis DP. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. BMJ. 2014;349:g4379.

    Article  Google Scholar 

  26. 26.

    Tan P, Wei S, Tang Z, Gao L, Zhang C, Nie P, et al. LDL-lowering therapy and the risk of prostate cancer: a meta-analysis of 6 randomized controlled trials and 36 observational studies. Sci Rep. 2016;6:24521.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

Funding: This study was supported by NIH 1K24CA160653 (S.J.F.), and by the American Institute for Cancer Research (E.H.A), and Irish Cancer Society John Fitzpatrick Fellowship (E.H.A).

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Correspondence to Stephen J. Freedland.

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Conflict of interest

The REDUCE study was funded by GlaxoSmithKline. Dr Castro-Santamaria is an employee of GlaxoSmithKline. Dr Andriole is a consultant for GlaxoSmithKline. The authors declare that they have no conflict of interest.

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

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