Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification.
Authors
Ho, Peh Joo
Ho, Weang Kee
Khng, Alexis J
Yeoh, Yen Shing
Tan, Benita Kiat-Tee
Tan, Ern Yu
Lim, Geok Hoon
Tan, Su-Ming
Tan, Veronique Kiak Mien
Yip, Cheng-Har
Mohd-Taib, Nur-Aishah
Wong, Fuh Yong
Lim, Elaine Hsuen
Ngeow, Joanne
Chay, Wen Yee
Leong, Lester Chee Hao
Yong, Wei Sean
Seah, Chin Mui
Tang, Siau Wei
Ng, Celene Wei Qi
Yan, Zhiyan
Lee, Jung Ah
Rahmat, Kartini
Islam, Tania
Hassan, Tiara
Tai, Mei-Chee
Khor, Chiea Chuen
Yuan, Jian-Min
Koh, Woon-Puay
Sim, Xueling
Dunning, Alison M
Bolla, Manjeet K
Teo, Soo-Hwang
Hartman, Mikael
Publication Date
2022-04-26Journal Title
BMC Med
ISSN
1741-7015
Publisher
BioMed Central
Volume
20
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Ho, P. J., Ho, W. K., Khng, A. J., Yeoh, Y. S., Tan, B. K., Tan, E. Y., Lim, G. H., et al. (2022). Overlap of high-risk individuals predicted by family history, and genetic and non-genetic breast cancer risk prediction models: implications for risk stratification.. BMC Med, 20 (1) https://doi.org/10.1186/s12916-022-02334-z
Abstract
BACKGROUND: Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear. METHODS: In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%. RESULTS: Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history. CONCLUSIONS: Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.
Keywords
Research Article, Breast cancer, Polygenic risk score, Gail model, Protein-truncating variants, Risk-based screening
Sponsorship
European Commission (16563)
National Cancer Institute (U19CA148065)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
Wellcome Trust (203477/Z/16/Z)
Identifiers
s12916-022-02334-z, 2334
External DOI: https://doi.org/10.1186/s12916-022-02334-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336472
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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