Journal article

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

Tu Nguyen-Dumont, James G Dowty, Jason A Steen, Anne-Laure Renault, Fleur Hammet, Maryam Mahmoodi, Derrick Theys, Amanda Rewse, Helen Tsimiklis, Ingrid M Winship, Graham G Giles, Roger L Milne, John L Hopper, Melissa C Southey

CANCERS | MDPI | Published : 2021


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 variant..

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Awarded by U.S. National Institute of Health

Awarded by U.S. National Cancer Institute

Awarded by NHMRC

Awarded by NHMRC European Union Collaborative Research Grant

Awarded by National Breast Cancer Foundation (BRA-STRAP)

Funding Acknowledgements

This work was funded by the U.S. National Institute of Health (grant number RO1CA159868). The ABCFR was supported in Australia by the National Health and Medical Research Council, the New South Wales Cancer Council, the Victorian Health Promotion Foundation, the Victorian Breast Cancer Research Consortium, Cancer Australia, and the National Breast Cancer Foundation. The six sites of the Breast Cancer Family Registry (BCFR) were supported by grant UM1 CA164920 from the U.S. National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. TN-D is a National Breast Cancer Foundation (Australia) Career Development Fellow (ECF-17-001). MCS is a National Health and Medical Research Council (NMHRC, Australia) Senior Research Fellow (APP1155163). This work was supported by an NHMRC Program grant (APP1074383), The National Breast Cancer Foundation (BRA-STRAP; NT-15-016), NHMRC European Union Collaborative Research Grant (APP1101400) and Monash University, Melbourne, Australia.