Impact of germline DNA repair gene variants on prognosis and treatment of men with advanced prostate cancer.

Autor: Hansen EB; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Karlsson Q; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Merson S; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Wakerell S; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Rageevakumar R; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Jensen JB; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Urology, Regional Hospital of West Jutland, Gødstrup Hospital, Gødstrup, Denmark., Borre M; Department of Urology, Aarhus University Hospital, Aarhus, Denmark., Kote-Jarai Z; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Eeles RA; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK.; Royal Marsden NHS Foundation Trust, London, UK., Sørensen KD; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark. kdso@clin.au.dk.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. kdso@clin.au.dk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Nov 06; Vol. 13 (1), pp. 19135. Date of Electronic Publication: 2023 Nov 06.
DOI: 10.1038/s41598-023-46323-5
Abstrakt: The clinical importance of germline variants in DNA repair genes (DRGs) is becoming increasingly recognized, but their impact on advanced prostate cancer prognosis remains unclear. A cohort of 221 newly diagnosed metastatic castration-resistant prostate cancer (mCRPC) patients were screened for pathogenic germline variants in 114 DRGs. The primary endpoint was progression-free survival (PFS) on first-line androgen signaling inhibitor (ARSI) treatment for mCRPC. Secondary endpoints were time to mCRPC progression on initial androgen deprivation therapy (ADT) and overall survival (OS). Twenty-seven patients (12.2%) carried a germline DRG variant. DRG carrier status was independently associated with shorter PFS on first-line ARSI [HR 1.72 (1.06-2.81), P = 0.029]. At initiation of ADT, DRG carrier status was independently associated with shorter progression time to mCRPC [HR 1.56, (1.02-2.39), P = 0.04] and shorter OS [HR 1.99, (1.12-3.52), P = 0.02]. Investigating the contributions of individual germline DRG variants on PFS and OS revealed CHEK2 variants to have little effect. Furthermore, prior taxane treatment was associated with worse PFS on first-line ARSI for DRG carriers excluding CHEK2 (P = 0.0001), but not for noncarriers. In conclusion, germline DRG carrier status holds independent prognostic value for predicting advanced prostate cancer patient outcomes and may potentially inform on optimal treatment sequencing already at the hormone-sensitive stage.
(© 2023. The Author(s).)
Databáze: MEDLINE
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