{"doi":"10.1158/1078-0432.c.6532764","title":"Data from Inherited Germline Cancer Susceptibility Gene Variants in Individuals with Non–Muscle-Invasive Bladder Cancer","abstract":"<div>AbstractPurpose:<p>Identification of inherited germline variants can guide personalized cancer screening, prevention, and treatment. Pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes are frequent among patients with locally advanced or metastatic urothelial carcinoma, but their prevalence and significance in patients with non–muscle-invasive bladder cancer (NMIBC), the most common form of urothelial carcinoma, is understudied.</p>Experimental Design:<p>Germline analysis was conducted on paired tumor/normal sequencing results from two distinct cohorts of patients initially diagnosed with NMIBC. Associations between clinicopathologic features and clinical outcomes with the presence of P/LP germline variants in ≥76 hereditary cancer predisposition genes were analyzed.</p>Results:<p>A similar frequency of P/LP germline variants were seen in our two NMIBC cohorts [12% (12/99) vs. 8.7% (10/115), <i>P</i> = 0.4]. In the combined analysis, P/LP germline variants were found only in patients with high-grade NMIBC (22/163), but none of the 46 patients with low-grade NMIBC (13.5% vs. 0%, <i>P</i> = 0.005). Fifteen (9.2%) patients with high-grade NMIBC had P/LP variants in DNA damage response genes, most within the nucleotide excision repair (<i>ERCC2/3</i>) and homologous recombination repair (<i>BRCA1, NBN, RAD50</i>) pathways. Contrary to prior reports in patients with NMIBC not receiving Bacillus Calmette-Guerin (BCG), P/LP germline variants were not associated with worse recurrence-free or progression-free survival in patients treated with BCG or with risk of developing upper tract urothelial carcinoma.</p>Conclusions:<p>Our results support offering germline counseling and testing for all patients with high-grade bladder cancer, regardless of initial tumor stage. Therapeutic strategies that target impaired DNA repair may benefit patients with high-grade NMIBC.</p></div>","journal":null,"year":2023,"id":405336,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8654,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":704740,"name":"Karissa Whiting","orcid":"0000-0002-4683-1868","position":1,"is_corresponding":false},{"id":626093,"name":"Preethi Srinivasan","orcid":"0000-0002-7137-3440","position":2,"is_corresponding":false},{"id":271416,"name":"Chaitanya Bandlamudi","orcid":"0000-0003-1108-4919","position":3,"is_corresponding":false},{"id":671902,"name":"Aliya Khurram","orcid":"0000-0003-3726-6382","position":4,"is_corresponding":false},{"id":74232,"name":"Vijai Joseph","orcid":"0000-0002-7933-151X","position":5,"is_corresponding":false},{"id":444445,"name":"Aleksandra Walasek","orcid":null,"position":6,"is_corresponding":false},{"id":934023,"name":"Emily Bochner","orcid":"0000-0002-3008-0262","position":7,"is_corresponding":false},{"id":345893,"name":"Timothy N. 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