Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study
Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown. Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cance...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | European Urology Open Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S266616832400226X |
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| author | Chiara Casadei Emanuela Scarpi Vincenza Conteduca Giorgia Gurioli Maria Concetta Cursano Nicole Brighi Cristian Lolli Giuseppe Schepisi Umberto Basso Giuseppe Fornarini Sara Bleve Alberto Farolfi Amelia Altavilla Salvatore Luca Burgio Emilio Francesco Giunta Caterina Gianni Alessia Filograna Paola Ulivi David Olmos Elena Castro Ugo De Giorgi |
| author_facet | Chiara Casadei Emanuela Scarpi Vincenza Conteduca Giorgia Gurioli Maria Concetta Cursano Nicole Brighi Cristian Lolli Giuseppe Schepisi Umberto Basso Giuseppe Fornarini Sara Bleve Alberto Farolfi Amelia Altavilla Salvatore Luca Burgio Emilio Francesco Giunta Caterina Gianni Alessia Filograna Paola Ulivi David Olmos Elena Castro Ugo De Giorgi |
| author_sort | Chiara Casadei |
| collection | DOAJ |
| description | Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown. Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cancer (mPCa) and analyzed the impact on response to therapy, survival, and time to castration resistance. Design, setting, and participants: In an observational prospective trial, 300 consecutive Italian mPCa patients, enrolled in the Meet-Uro-10 trial from three academic Italian centers, were recruited between 2017 and 2019 and were screened for gDDR mutations in 107 genes. Outcome measurements and statistical analysis: The primary endpoint was to assess the prevalence of gDDR mutations in the Italian population of patients with mPCa. The secondary endpoints included the association of gDDR subgroups with metastatic onset, Gleason score, and time to castration resistance. Results and limitations: We identified 297 valuable patients. Forty-six patients had a pathogenic/likely pathogenic variant (15.5%, 95% confidence interval: 11.4–19.6): the more frequent was gBRCA2 found in nine cases (3%), followed by gATM in five cases (1.7%). In patients without mutations, longer median overall survival was observed with the sequence docetaxel-androgen receptor signaling inhibitor (ARSI) than with the sequence ARSI-docetaxel (87.9 vs 42 mo, p = 0.0001). In a univariate analysis, the median time to castration resistance in gDDR mutated patients was 19.8 mo, versus 23.7 mo in no mutated patients (p = 0.024). There were no associations of gDDR subgroups with metastatic onset and Gleason score ≥8. In our cohort, variants of unknown significance in gDDR genes were found in 80 patients and might have a prognostic relevance. Conclusions: The study reported the prevalence of gDDR in the Italian population. The presence of gBRCA2 mutations correlates with a shorter time to the onset of castration resistance disease. Patient summary: The prevalence of gBRCA2 in the Italian population is 3%, which is similar to that in the Spanish population, identifying similarities between people of the Western Mediterranean area. |
| first_indexed | 2024-03-07T23:52:27Z |
| format | Article |
| id | doaj.art-da61ee9b940b4381ac3aa92030e5b551 |
| institution | Directory Open Access Journal |
| issn | 2666-1683 |
| language | English |
| last_indexed | 2024-03-07T23:52:27Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Urology Open Science |
| spelling | doaj.art-da61ee9b940b4381ac3aa92030e5b5512024-02-19T04:14:01ZengElsevierEuropean Urology Open Science2666-16832024-03-01614451Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 StudyChiara Casadei0Emanuela Scarpi1Vincenza Conteduca2Giorgia Gurioli3Maria Concetta Cursano4Nicole Brighi5Cristian Lolli6Giuseppe Schepisi7Umberto Basso8Giuseppe Fornarini9Sara Bleve10Alberto Farolfi11Amelia Altavilla12Salvatore Luca Burgio13Emilio Francesco Giunta14Caterina Gianni15Alessia Filograna16Paola Ulivi17David Olmos18Elena Castro19Ugo De Giorgi20IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyPoliclinico Riuniti, University of Foggia, Foggia, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIstituto Oncologico Veneto IRCCS, Padova, ItalySan Martino Hospital, Genova, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, ItalyHospital Universitario 12 de Octubre, Madrid, SpainInstituto de Investigación Biomédica de Málaga (IBIMA), Málaga, SpainIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy; Corresponding author. IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, via Piero Maroncelli 40, 47014 Meldola (FC), Italy. Tel. +39 0543-739100.Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown. Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cancer (mPCa) and analyzed the impact on response to therapy, survival, and time to castration resistance. Design, setting, and participants: In an observational prospective trial, 300 consecutive Italian mPCa patients, enrolled in the Meet-Uro-10 trial from three academic Italian centers, were recruited between 2017 and 2019 and were screened for gDDR mutations in 107 genes. Outcome measurements and statistical analysis: The primary endpoint was to assess the prevalence of gDDR mutations in the Italian population of patients with mPCa. The secondary endpoints included the association of gDDR subgroups with metastatic onset, Gleason score, and time to castration resistance. Results and limitations: We identified 297 valuable patients. Forty-six patients had a pathogenic/likely pathogenic variant (15.5%, 95% confidence interval: 11.4–19.6): the more frequent was gBRCA2 found in nine cases (3%), followed by gATM in five cases (1.7%). In patients without mutations, longer median overall survival was observed with the sequence docetaxel-androgen receptor signaling inhibitor (ARSI) than with the sequence ARSI-docetaxel (87.9 vs 42 mo, p = 0.0001). In a univariate analysis, the median time to castration resistance in gDDR mutated patients was 19.8 mo, versus 23.7 mo in no mutated patients (p = 0.024). There were no associations of gDDR subgroups with metastatic onset and Gleason score ≥8. In our cohort, variants of unknown significance in gDDR genes were found in 80 patients and might have a prognostic relevance. Conclusions: The study reported the prevalence of gDDR in the Italian population. The presence of gBRCA2 mutations correlates with a shorter time to the onset of castration resistance disease. Patient summary: The prevalence of gBRCA2 in the Italian population is 3%, which is similar to that in the Spanish population, identifying similarities between people of the Western Mediterranean area.http://www.sciencedirect.com/science/article/pii/S266616832400226XDNA damage repair gene mutationsGermline BRCA2 mutationsMetastatic prostate cancerPrecision medicine |
| spellingShingle | Chiara Casadei Emanuela Scarpi Vincenza Conteduca Giorgia Gurioli Maria Concetta Cursano Nicole Brighi Cristian Lolli Giuseppe Schepisi Umberto Basso Giuseppe Fornarini Sara Bleve Alberto Farolfi Amelia Altavilla Salvatore Luca Burgio Emilio Francesco Giunta Caterina Gianni Alessia Filograna Paola Ulivi David Olmos Elena Castro Ugo De Giorgi Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study European Urology Open Science DNA damage repair gene mutations Germline BRCA2 mutations Metastatic prostate cancer Precision medicine |
| title | Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study |
| title_full | Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study |
| title_fullStr | Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study |
| title_full_unstemmed | Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study |
| title_short | Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study |
| title_sort | inherited mutations in dna damage repair genes in italian men with metastatic prostate cancer results from the meet uro 10 study |
| topic | DNA damage repair gene mutations Germline BRCA2 mutations Metastatic prostate cancer Precision medicine |
| url | http://www.sciencedirect.com/science/article/pii/S266616832400226X |
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