{"doi":"10.3390/cancers13061378","title":"Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants in CHEK2: Findings from the Australian Breast Cancer Family Registry","abstract":"Case-control studies of breast cancer have consistently shown that pathogenic variants in CHEK2 are associated with about a 3-fold increased risk of breast cancer. Information about the recurrent protein-truncating variant CHEK2 c.1100delC dominates this estimate. There have been no formal estimates of age-specific cumulative risk of breast cancer for all CHEK2 pathogenic (including likely pathogenic) variants combined. We conducted a population-based case-control-family study of pathogenic CHEK2 variants (26 families, 1071 relatives) and estimated the age-specific cumulative risk of breast cancer using segregation analysis. The estimated hazard ratio for carriers of pathogenic CHEK2 variants (combined) was 4.9 (95% CI 2.5–9.5) relative to non-carriers. The HR for carriers of the CHEK2 c.1100delC variant was estimated to be 3.5 (95% CI 1.02–11.6) and the HR for carriers of all other CHEK2 variants combined was estimated to be 5.7 (95% CI 2.5–12.9). The age-specific cumulative risk of breast cancer was estimated to be 18% (95% CI 11–30%) and 33% (95% CI 21–48%) to age 60 and 80 years, respectively. These findings provide important information for the clinical management of breast cancer risk for women carrying pathogenic variants in CHEK2.","journal":"Cancers","year":2021,"id":190752,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9371,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":383881,"name":"James G. Dowty","orcid":"0000-0003-2383-0886","position":1,"is_corresponding":false},{"id":523469,"name":"Jason A. Steen","orcid":"0000-0003-1351-5815","position":2,"is_corresponding":false},{"id":724256,"name":"Anne‐Laure Renault","orcid":"0000-0001-6321-3458","position":3,"is_corresponding":false},{"id":524345,"name":"Fleur Hammet","orcid":null,"position":4,"is_corresponding":false},{"id":523471,"name":"Maryam Mahmoodi","orcid":"0000-0002-9013-607X","position":5,"is_corresponding":false},{"id":524346,"name":"Derrick Theys","orcid":null,"position":6,"is_corresponding":false},{"id":755570,"name":"Amanda Rewse","orcid":null,"position":7,"is_corresponding":false},{"id":523472,"name":"Helen Tsimiklis","orcid":"0009-0006-0297-5460","position":8,"is_corresponding":false},{"id":383883,"name":"Ingrid Winship","orcid":"0000-0001-8535-6003","position":9,"is_corresponding":false},{"id":55326,"name":"Graham G. Giles","orcid":"0000-0003-4946-9099","position":10,"is_corresponding":false},{"id":34653,"name":"Roger L. Milne","orcid":"0000-0001-5764-7268","position":11,"is_corresponding":false},{"id":228672,"name":"John L. Hopper","orcid":"0000-0002-8567-173X","position":12,"is_corresponding":false},{"id":55360,"name":"Melissa C. Southey","orcid":"0000-0002-6313-9005","position":13,"is_corresponding":false},{"id":291310,"name":"Tú Nguyen‐Dumont","orcid":"0000-0002-6217-0182","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:49:26.966524Z","pmid":"33803639","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":[]}