{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:31:47Z","timestamp":1786977107087,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJUI Compass"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The contribution of germline DNA repair gene (gDRG) variants to bladder cancer (BC) susceptibility and progression is still poorly defined, particularly in European populations. This study aims to evaluate the prevalence and clinical implications of germline homologous recombination repair (HRR) gene variants in BC patients of European ancestry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective case\u2013control study, 75\u2009BC patients attending follow\u2010up at a single tertiary centre were screened for germline variants in 20 gDRGs. Patients were included regardless of disease stage and classified by pathogenicity (Class 3\u20135). Clinical characteristics and outcomes were compared between variant\u2010positive and variant\u2010negative patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 75 eligible patients, 72 underwent successful germline sequencing. A total of 23 patients (30.6%) harboured at least one pathogenic, likely pathogenic, or VUS variant. The most frequently altered genes included\n                      <jats:italic>ATM<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096),\n                      <jats:italic>ATR<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094),\n                      <jats:italic>BARD1<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094),\n                      <jats:italic>CHEK2<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093) and\n                      <jats:italic>PMS2<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093). Eight patients (34.7%) had multiple variants, and one carried three variants. Notably, 25.8% of NMIBC and 50% of MIBC patients had gDRG variants. Moreover, 30% of patients with low\u2010grade G1 disease harboured at least one variant. Patients with gDRG variants had a higher rate of histopathological variants (34.8% vs. 13.5%) and underwent radical cystectomy at a younger age (60 vs. 75\u2009years,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Germline HRR variants are prevalent in BC patients and may influence disease aggressiveness and treatment decisions. These findings support broader implementation of germline testing in BC and warrant further validation in larger cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bco2.70077","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T05:04:37Z","timestamp":1758863077000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Germline homologous recombination repair (gHRR) variants in bladder cancer: Preliminary evidence and clinical implications"],"prefix":"10.1002","volume":"6","author":[{"given":"Rodolfo","family":"Hurle","sequence":"first","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Capalbo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"},{"name":"Medical Genetics and RNA Biology Laboratory IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3939-4521","authenticated-orcid":false,"given":"Giovanni","family":"Lughezzani","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"},{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2 Maria","family":"Buffi","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"},{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Sormani","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0273-7593","authenticated-orcid":false,"given":"Alessio","family":"Finocchiaro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Saita","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8456-6495","authenticated-orcid":false,"given":"Marco","family":"Paciotti","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"},{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Fasulo","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"},{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Cavalli","sequence":"additional","affiliation":[{"name":"Laboratory Analysis Unit IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Laboratory Analysis Unit IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Benetti","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo","family":"Avolio","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Asselta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"},{"name":"Medical Genetics and RNA Biology Laboratory IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Sold\u00e0","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Pieve Emanuele Italy"},{"name":"Medical Genetics and RNA Biology Laboratory IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Casale","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4411-3715","authenticated-orcid":false,"given":"Massimo","family":"Lazzeri","sequence":"additional","affiliation":[{"name":"Department of Urology IRCCS\u2010Humanitas Research Hospital  Rozzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-024-04949-8"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2023.03.029"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60264-1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2020-004128"},{"key":"e_1_2_11_6_1","unstructured":"Carlo Maria Isabel Zhang Liying Mandelker Diana Vijai Joseph Cipolla Catharine Kline Robson Mark E. Funt Samuel Hakimi A. Ari Iyer Gopa Rosenberg Jonathan E. Coleman Jonathan Solit David B. Offit Kenneth andBajorin Dean F.Cancer predisposing germline mutations in patients (pts) with urothelial cancer (UC) of the renal pelvis (R\u2010P) ureter (U) and bladder (B)."},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077232"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.5_suppl.741"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0720-x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.14370"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894-022-01141-1"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2021.05.002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bco2.252"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603144"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_16_1","article-title":"GSTM1 and NAT2 polymorphisms and colon, lung and bladder cancer risk: A case\u2010control study","author":"Zupa A","year":"2009","journal-title":"Anticancer Research"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-00313-1"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201855"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13174385"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2025.104543"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.5_suppl.683"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-1006"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.5_suppl.849"}],"container-title":["BJUI Compass"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bco2.70077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T23:47:07Z","timestamp":1764719227000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjui-journals.onlinelibrary.wiley.com\/doi\/10.1002\/bco2.70077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":22,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/bco2.70077"],"URL":"https:\/\/doi.org\/10.1002\/bco2.70077","archive":["Portico"],"relation":{},"ISSN":["2688-4526","2688-4526"],"issn-type":[{"value":"2688-4526","type":"print"},{"value":"2688-4526","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]},"assertion":[{"value":"2025-07-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70077"}}