Journal article
Rare Germline Variants Are Associated with Rapid Biochemical Recurrence After Radical Prostate Cancer Treatment: A Pan Prostate Cancer Group Study
D Burns, E Anokian, EJ Saunders, RG Bristow, M Fraser, J Reimand, T Schlomm, G Sauter, B Brors, J Korbel, J Weischenfeldt, SM Waszak, NM Corcoran, CH Jung, BJ Pope, CM Hovens, G Cancel-Tassin, O Cussenot, M Loda, C Sander Show all
European Urology | Published : 2022
Open access
Abstract
Background: Germline variants explain more than a third of prostate cancer (PrCa) risk, but very few associations have been identified between heritable factors and clinical progression. Objective: To find rare germline variants that predict time to biochemical recurrence (BCR) after radical treatment in men with PrCa and understand the genetic factors associated with such progression. Design, setting, and participants: Whole-genome sequencing data from blood DNA were analysed for 850 PrCa patients with radical treatment from the Pan Prostate Cancer Group (PPCG) consortium from the UK, Canada, Germany, Australia, and France. Findings were validated using 383 patients from The Cancer Genome A..
View full abstractGrants
Awarded by NIHR Oxford Biomedical Research Centre
Funding Acknowledgements
Funding/Support and role of the sponsor: We acknowledge support from Cancer Research UK C5047/A14835/A22530/A17528, C309/A11566, C368/A6743, A368/A7990, and C14303/A17197 (Zsofia Kote-Jarai, S. Mer-son, Niall M. Corcoran, S.E., D.L., T. Dadaev, M.A., E.B., J.B., G.A., P.W., B.A.-L., Daniel S. Brewer, Colin S. Cooper, and Rosalind A. Eeles) ; the Dallaglio Foundation (CR-UK Prostate Cancer ICGC Project and Pan Prostate Cancer Group) , PC-UK/Movember (Zsofia Kote-Jarai) , the NIHR support to the Biomedical Research Centre at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust (Zsofia Kote-Jarai, N.D., S. Merson, Niall M. Corcoran, S.E., D.L., T. Dadaev, S. Thomas, M.A., E.B., Christopher S. Foster, N.L., D.N., V.K., N.A., P.K., C.O., D.C., A.T., E.M., E.R., T. Dudderidge, S. Hazell, J.B., G.A., P.W., B.A.-L., Daniel S. Brewer, Colin S. Cooper, and Ros-alind A. Eeles) , Cancer Research UK funding to the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust CRUK Centre, the National Cancer Research Institute (National Institute of Health Research (NIHR) Collaborative Study (grant G0500966/75466; D.E.N. and Vincent Gnanapragasam) : ?Prostate Cancer: Mechanisms of Progres-sion and Treatment (PROMPT) ?, the Li Ka Shing Foundation (David C. Wedge and Dan J. Woodcock) , Canadian Institutes of Health Research (CIHR) Project Grant (J?ri Reimand) , and the Academy of Finland and Can-cer Society of Finland (G.S.B.) . D.M.B. is supported by Orchid. C.V.?s aca-demic time was supported by the NIHR Oxford Biomedical Research Centre (Molecular Diagnostics Theme/Multimodal Pathology subtheme) . We also acknowledge support from the Bob Champion Cancer Trust, the Masonic Charitable Foundation successor to the Grand Charity, the King Family, and the Stephen Hargrave Trust (Colin S. Cooper and Daniel S. Brewer) . We acknowledge core facilities provided by CRUK funding to the CRUK ICR Centre, the CRUK Cancer Therapeutics Unit, and support for canSAR C35696/A23187 (P.W. and G.A.) . We would like to acknowl-edge the D.J. Fielding Medical Research Trust for its support. Support for analysis of the Australian samples was provided through the PRECEPT program grant, cofunded by Movember and the Australian Federal Government (PI Niall M. Corcoran) as well as NHMRC projects grants #10413 (CIs Chris M. Hovens, Niall M. Corcoran, and R.E.A.) and #1104010 (CIs Chris M. Hovens and Niall M. Corcoran) . Bernard J. Pope was supported by a Victorian Health and Medical Research Fellowship from the Department of Health and Human Services in the State of Victo-ria. Niall M. Corcoran was supported by a David Bickart Clinician Researcher Fellowship from the Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, and more recently by a Movember - Distinguished Gentleman?s Ride Clinician Scientist Award through the Prostate Cancer Foundation of Australia?s Research Program. The French Prostate ICGC project was founded by Institut National de la Sant? et de la Recherche M?dicale (INSERM) and Institut National du Cancer (INCa) , grant INSERM CV_2011/023 (C18) , with additional support from LYric (grant INCa-4662) . The PPCG project at Weill Cornell Medicine is sup-ported by NCI P50CA211024, DoD PC160357, DoD PC180582, and the-Prostate Cancer Foundation.