Maria I Van Rompay1, Keith R Solomon2, J Curtis Nickel3, Gayatri Ranganathan4, Philip W Kantoff5, John B McKinlay6. 1. HealthCore-NERI, 480 Pleasant Street, Watertown, MA 02472, USA. Electronic address: mvanrompay@neriscience.com. 2. 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: drmungo@yahoo.com. 3. Department of Urology, Queen's University, Kingston, ON, Canada. Electronic address: jcn@queensu.ca. 4. HealthCore-NERI, 480 Pleasant Street, Watertown, MA 02472, USA. Electronic address: GRanganathan@neriscience.com. 5. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: kantoff@mskcc.org. 6. HealthCore-NERI, 480 Pleasant Street, Watertown, MA 02472, USA; Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: jandsmckinlay@gmail.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Authors: Sebastian Schneeweiss; Amanda R Patrick; Til Stürmer; M Alan Brookhart; Jerry Avorn; Malcolm Maclure; Kenneth J Rothman; Robert J Glynn Journal: Med Care Date: 2007-10 Impact factor: 2.983
Authors: Elizabeth A Platz; Michael F Leitzmann; Kala Visvanathan; Eric B Rimm; Meir J Stampfer; Walter C Willett; Edward Giovannucci Journal: J Natl Cancer Inst Date: 2006-12-20 Impact factor: 13.506
Authors: C Baigent; A Keech; P M Kearney; L Blackwell; G Buck; C Pollicino; A Kirby; T Sourjina; R Peto; R Collins; R Simes Journal: Lancet Date: 2005-09-27 Impact factor: 79.321
Authors: Eric J Jacobs; Carmen Rodriguez; Elizabeth B Bain; Yiting Wang; Michael J Thun; Eugenia E Calle Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-10-30 Impact factor: 4.254
Authors: E Dawn Flick; Laurel A Habel; K Arnold Chan; Stephen K Van Den Eeden; Virginia P Quinn; Reina Haque; Endel J Orav; John D Seeger; Marianne C Sadler; Charles P Quesenberry; Barbara Sternfeld; Steven J Jacobsen; Rachel A Whitmer; Bette J Caan Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-10-30 Impact factor: 4.254
Authors: Abhishek Kumar; Paul Riviere; Elaine Luterstein; Vinit Nalawade; Lucas Vitzthum; Reith R Sarkar; Alex K Bryant; John P Einck; Arno J Mundt; James D Murphy; Brent S Rose Journal: Prostate Cancer Prostatic Dis Date: 2020-02-06 Impact factor: 5.554
Authors: Fei Chen; Peggy Wan; Lynne R Wilkens; Loïc Le Marchand; Christopher A Haiman Journal: Cancer Epidemiol Biomarkers Prev Date: 2022-05-04 Impact factor: 4.254
Authors: Khaldoun S Abdelwahed; Abu Bakar Siddique; Mohammed H Qusa; Judy Ann King; Soumaya Souid; Zakaria Y Abd Elmageed; Khalid A El Sayed Journal: ACS Pharmacol Transl Sci Date: 2021-10-05
Authors: Lisa M Butler; Peter J Meikle; Lisa G Horvath; Hui-Ming Lin; Kevin Huynh; Manish Kohli; Winston Tan; Arun A Azad; Nicole Yeung; Kate L Mahon; Blossom Mak; Peter D Sutherland; Andrew Shepherd; Natalie Mellett; Maria Docanto; Corey Giles; Margaret M Centenera Journal: Prostate Cancer Prostatic Dis Date: 2021-03-21 Impact factor: 5.554
Authors: Xiang-Lin Tan; Jian-Yu E; Yong Lin; Timothy R Rebbeck; Shou-En Lu; Mingyi Shang; William K Kelly; Anthony D'Amico; Mark N Stein; Lanjing Zhang; Thomas L Jang; Isaac Yi Kim; Kitaw Demissie; Anna Ferrari; Grace Lu-Yao Journal: Cancer Med Date: 2020-02-08 Impact factor: 4.452