{"doi":"10.1101/2025.01.21.25320918","title":"Homologous recombination deficiency in ovarian high-grade serous carcinoma by self-reported race","abstract":"<h4>ABSTRACT</h4> <h4>Background</h4> Approximately half of ovarian high-grade serous carcinomas (HGSC) have homologous recombination deficiency (HRD). However, HRD is not well-characterized in Black individuals. <h4>Objective</h4> To characterize HGSC HRD by self-reported race and evaluate whether differences in HRD are associated with ovarian cancer mortality. <h4>Study population</h4> Cohort study using data collected from two population-based case-control studies of ovarian cancer. Cases were selected based on self-reported race (178 Black, 123 White) and pathologically-confirmed HGSC. <h4>Exposures</h4> HRD features identified using matched tumor-normal whole-exome DNA sequencing and categorized as germline or somatic variants in homologous recombination pathway genes, or the SBS3 HRD-associated signature. <h4>Outcomes</h4> Median difference and 95% confidence intervals (CI) for age at diagnosis and tumor mutation burden, and age and stage-adjusted hazard ratios (HR) and 95%CIs for survival, comparing individuals with an HRD feature to those without, separately by self-reported race. <h4>Results</h4> More of the germline and somatic variants detected among Black individuals compared with White individuals were unannotated or variants of uncertain significance (VUS; germline 65% versus 45%; somatic 62% versus 50%, respectively). While the prevalences of many HRD features were similar between Black individuals and White individuals, Black individuals had a higher prevalence of the HRD signature identified using de novo mutational signature analysis (40% versus 29%) and germline BRCA2 variants (8% versus 2%) compared with White individuals. We observed that among Black individuals, BRCA2 variants were associated with better survival (somatic HR=0.23, 95%CI 0.07–0.76; germline HR=0.48, 95%CI 0.22–1.03), while germline BRCA1 variants were associated with worse survival (HR=2.11, 95%CI 1.14–3.88). When we restricted to VUS and unannotated variants, we observed similar associations with survival for BRCA 2 among Black individuals (somatic HR=0.18, 95%CI 0.04-0.75; germline HR=0.40, 95%CI 0.15–1.09). <h4>Conclusions and Relevance</h4> HRD testing informs precision-based medicine approaches that improve outcomes, but a higher proportion of VUS among Black individuals may complicate referral for such care. Our findings emphasize the importance of recruiting diverse individuals in genomics research and better characterizing VUS.","journal":"medRxiv","year":2025,"id":6214,"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":0.2799,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-28","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":300,"name":"Courtney E. Johnson","orcid":"0000-0003-4980-3499","position":1,"is_corresponding":false},{"id":297,"name":"Mollie  E. Barnard","orcid":"0000-0002-4843-4655","position":2,"is_corresponding":false},{"id":4464,"name":"Lindsay  J. Collin","orcid":"0000-0003-0170-2592","position":4,"is_corresponding":false},{"id":4465,"name":"David  A. Nix","orcid":"0009-0002-3383-8582","position":5,"is_corresponding":false},{"id":58196,"name":"Chad Huff","orcid":null,"position":6,"is_corresponding":false},{"id":58197,"name":"Andy Berchuck","orcid":null,"position":7,"is_corresponding":false},{"id":304,"name":"Lucas  A. Salas","orcid":"0000-0002-2279-4097","position":8,"is_corresponding":false},{"id":306,"name":"Jeffrey  R. Marks","orcid":"0000-0002-2054-5468","position":10,"is_corresponding":false},{"id":305,"name":"Lauren C. Peres","orcid":"0000-0002-6620-8600","position":11,"is_corresponding":false},{"id":309,"name":"Jennifer Anne Doherty","orcid":"0000-0002-1454-8187","position":12,"is_corresponding":false},{"id":307,"name":"Joellen M. Schildkraut","orcid":"0000-0002-0990-9339","position":13,"is_corresponding":false},{"id":296,"name":"Natalie R. Davidson","orcid":"0000-0002-1745-8072","position":14,"is_corresponding":false},{"id":308,"name":"Casey S. Greene","orcid":"0000-0001-8713-9213","position":15,"is_corresponding":false},{"id":4463,"name":"Katherine A. Lawson-Michod","orcid":"0000-0002-0187-9702","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}