Statins have demonstrated protection against aggressive/late-stage and/or lethal prostate cancer (PC), but prior studies are limited by small populations, short follow-up and unequal health-care access. Research has not demonstrated that non-statin lipid-lowering medications (NSLLMs) provide a similar benefit, which would support a cholesterol-based mechanism. We sought to rigorously test the hypothesis that cholesterol-lowering drugs affect PC incidence and severity.
A retrospective cohort study was conducted by abstracting prescription and health service records for 249,986 Saskatchewan men aged ≥40 years between January 1, 1990 and December 31, 2014 and comparing first-time statin and NSLLM users with age-matched non-users and glaucoma medication (GM) users for PC incidence, metastases at diagnosis and PC mortality using Cox proportional hazards regression.
In comparing statin users to non-users, a weak association was detected with increased PC incidence (hazard ratio [HR] 1.07, 95% confidence interval [CI]: 1.02-1.12) that disappeared when compared with GM users. Substantial protective associations were observed between statin use and metastatic PC and PC mortality (HRs 0.69, 95% CI: 0.61-0.79 and 0.73, 95% CI: 0.66-0.81, respectively), which were stronger when compared with GM use (HRs 0.52, 95% CI: 0.40-0.68 and 0.51, 95% CI: 0.41-0.63, respectively). Similar associations were found for NSLLM versus GM for metastatic PC (HR 0.57, 95% CI: 0.41-0.79) and PC mortality (HR 0.66, 95% CI: 0.51-0.85).
Our analyses provide one of the more comprehensive findings to date that statins may reduce risk of metastatic PC and PC mortality, and the first to demonstrate that NSLLM have similar effects, supporting a cholesterol-based mechanism.
European journal of cancer (Oxford, England : 1990). 2019 Mar 05 [Epub ahead of print]
Maria I Van Rompay, Keith R Solomon, J Curtis Nickel, Gayatri Ranganathan, Philip W Kantoff, John B McKinlay
HealthCore-NERI, 480 Pleasant Street, Watertown, MA 02472, USA. Electronic address: ., Department of Orthopaedic Surgery, Harvard Medical School, Boston Children's Hospital, Boston, MA 02115, USA; Department of Urology, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: ., Department of Urology, Queen's University, Kingston, ON, Canada. Electronic address: ., HealthCore-NERI, 480 Pleasant Street, Watertown, MA 02472, USA. Electronic address: ., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: ., HealthCore-NERI, 480 Pleasant Street, Watertown, MA 02472, USA; Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: .