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

Cancers

JohnL. Hopper¹  JamesG. Dowty¹  Maryam Mahmoodi²  Tú Nguyen-Dumont²  Helen Tsimiklis²  Derrick Theys²  Fleur Hammet²  RogerL. Milne²  Anne-Laure Renault²  JasonA. Steen²  MelissaC. Southey²  GrahamG. Giles²  Amanda Rewse²  IngridM. Winship³ 

[1] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Victoria 3010, Australia;Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Victoria 3168, Australia;Royal Melbourne Hospital, Parkville, Victoria 3050, Australia;

关键词: CHEK2;    breast cancer;    predisposition;    genetic risk factors;    age-specific cumulative risk;    penetrance;   

DOI  :  10.3390/cancers13061378

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown