Association of statin use with risk of Gleason score-specific prostate cancer: A hospital-based cohort study

Cancer Med. 2019 Dec;8(17):7399-7407. doi: 10.1002/cam4.2500. Epub 2019 Oct 8.

Abstract

Background: Conflicting evidence suggests that statins act chemopreventively against prostate cancer (PCa). Whether the association of statin use with PCa risk is Gleason score-dependent, time-, dose-respondent is not well studied.

Methods: We conducted a cohort study at a tertiary hospital in the Southeastern US using longitudinal data of electronic medical records (EMR) from 1994 to 2016. Only cancer-free men aged >18 years at baseline with follow-up time of ≥12 months were included. Time-dependent Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).

Results: Among 13 065 men, 2976 were diagnosed with PCa over median follow-up of 6.6 years. Statin use was associated with lower risk of both Gleason low- (score <7: aHR, 0.85; 95% CI, 0.74-0.96) and high-grade PCa (score ≥7: aHR, 0.54; 95% CI, 0.42-0.69). The protective association was observed only when statins had been used for a relatively longer duration (≥11 months) or higher dose (≥121 defined daily doses), and were more pronounced for PCa of higher Gleason score (<7: aHR, 0.85, 95% CI, 0.74-0.96; 7 [3 + 4]: aHR, 0.62, 95% CI, 0.43-0.90; 7 [4 + 3]: aHR, 0.49, 95% CI, 0.29-0.82; 8: aHR, 0.60, 95% CI, 0.37-0.96; 9-10: aHR, 0.24, 95% CI, 0.11-0.54). Lipophilic statins (aHR, 0.83; 95% CI, 0.72-0.95) might be more protective than hydrophilic statins (aHR, 0.91, 95% CI, 0.63-1.33) against PCa.

Conclusion: Statin use might be associated with reduced PCa risk only when used for a relatively longer duration, and the risk reduction was higher for PCa of higher Gleason score.

Keywords: Gleason score; dose-response; lipophilicity; prostate cancer; statins.

MeSH terms

  • Aged
  • Electronic Health Records / statistics & numerical data
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prostatic Neoplasms / epidemiology*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / prevention & control
  • Risk Factors
  • Southeastern United States / epidemiology
  • Tertiary Care Centers / statistics & numerical data
  • Time Factors

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors