Article

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

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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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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).

Author information

Affiliations

  1. Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    • Juzar Jamnagerwalla
    • , Adriana C. Vidal
    • , Michael R. Freeman
    •  & Stephen J. Freedland
  2. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA

    • Lauren E. Howard
  3. Surgery Section, Durham VA Medical Center, Durham, NC, USA

    • Lauren E. Howard
    •  & Stephen J. Freedland
  4. Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Emma H. Allott
  5. Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland

    • Emma H. Allott
  6. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA

    • Emma H. Allott
  7. Mayo Clinic, Department of Urology, Rochester, MN, USA

    • Daniel M. Moreira
  8. GlaxoSmithKline Inc., R&D, King of Prussia, PA, USA

    • Ramiro Castro-Santamaria
  9. Washington University School of Medicine in St. Louis, St. Louis, MO, USA

    • Gerald L. Andriole

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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.

Corresponding author

Correspondence to Stephen J. Freedland.

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