دورية أكاديمية
Impact of germline DNA repair gene variants on prognosis and treatment of men with advanced prostate cancer
| العنوان: | Impact of germline DNA repair gene variants on prognosis and treatment of men with advanced prostate cancer |
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| المؤلفون: | Hansen, Emma B., Karlsson, Questa, Merson, Susan, Wakerell, Sarah, Rageevakumar, Reshma, Jensen, Jørgen B., Borre, Michael, Kote-Jarai, Zsofia, Eeles, Rosalind A., Sørensen, Karina D. |
| المساهمون: | Novo Nordisk Fonden, Kræftens Bekæmpelse, Harboefonden, The Graduate School of Health, Aarhus University, Christian og Ottilia Brorsons Travel Grant, Rosetrees Trust, Cancer Research UK, Prostate Cancer UK |
| المصدر: | Scientific Reports ; volume 13, issue 1 ; ISSN 2045-2322 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Multidisciplinary |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41598-023-46323-5 |
| الإتاحة: | https://doi.org/10.1038/s41598-023-46323-5Test https://www.nature.com/articles/s41598-023-46323-5.pdfTest https://www.nature.com/articles/s41598-023-46323-5Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.FB00E779 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41598-023-46323-5 |
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