{"doi":"10.1101/2020.02.21.958256","title":"Prevalence of pathogenic variants in DNA damage response genes in patients undergoing cancer risk assessment and reporting a personal history of early-onset renal cancer","abstract":"ABSTRACT Purpose Pathogenic variants (PVs) in a number of genes are known to increase the risk of hereditary renal cancer (hRC). However, many early-onset RC (eoRC) patients undergoing genetic testing lack PVs in hRC genes; thus, their genetic risk remains undefined. To determine if PVs in DNA damage response (DDR) genes are enriched in a convenience sample of eoRC patients undergoing genetic testing. Materials and Methods Retrospective review of results for 844 unselected eoRC patients, undergoing genetic testing with a multi-gene cancer panel by Ambry Genetics [between July 2012 and December 2016]. The patients were tested with CancerNext and/or CancerNext Expanded panels for a variety of indications. Identified PVs were compared with patient characteristics. Results Mean age of RC diagnosis was 48 years [range 24-60]. In addition to eoRC, 57.9% patients tested reported at least one additional cancer; breast cancer being the most common (40.1% of females, 2.5% of males). PVs in cancer risk genes were identified in 12.8% of patients—3.7% in RC-specific genes, and 8.55% in DDR genes. DDR gene PVs were most commonly identified in CHEK2, BRCA1/2 , and ATM . Among the 2.1% of patients with a BRCA1/2 PV, <50% reported a personal history of hereditary breast/ovarian-associated cancer. No association between age of RC diagnosis, and prevalence of PVs in RC-specific or DDR genes was observed. Conclusions Multi-gene panel testing including DDR genes may provide a more comprehensive risk assessment in unselected eoRC patients, and their families. Validation in larger datasets is needed to characterize the association with eoRC.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":128981,"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":0.9639,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":484197,"name":"Elena V. Demidova","orcid":"0000-0003-2065-2551","position":1,"is_corresponding":false},{"id":484198,"name":"Randy W. Lesh","orcid":"0000-0003-4150-4363","position":2,"is_corresponding":false},{"id":484199,"name":"Lily Hoang","orcid":"0000-0002-0582-0900","position":3,"is_corresponding":false},{"id":74278,"name":"Marcy E. Richardson","orcid":"0000-0002-4626-4920","position":4,"is_corresponding":false},{"id":484200,"name":"Andrea Forman","orcid":"0000-0003-4782-8908","position":5,"is_corresponding":false},{"id":78637,"name":"Lisa Kessler","orcid":"0009-0003-9245-4949","position":6,"is_corresponding":false},{"id":320538,"name":"Virginia Speare","orcid":"0000-0003-4773-9411","position":7,"is_corresponding":false},{"id":241847,"name":"Erica A. Golemis","orcid":"0000-0003-3618-3673","position":8,"is_corresponding":false},{"id":254342,"name":"Michael J. Hall","orcid":"0000-0003-4515-3409","position":9,"is_corresponding":false},{"id":309116,"name":"Mary B. Daly","orcid":"0000-0002-7490-6038","position":10,"is_corresponding":false},{"id":484201,"name":"Sanjeevani Arora","orcid":"0000-0002-8273-589X","position":11,"is_corresponding":false},{"id":241839,"name":"Tiffiney R. Hartman","orcid":"0000-0002-9887-5002","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:42.522809Z","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":[]}