BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors.
Authors
Wilcox, Amber N
Carver, Tim
Hartley, Simon
Babb, Chantal Louiza
Izquierdo, Angel
Simard, Jacques
Schmidt, Marjanka K
Chatterjee, Nilanjan
Garcia-Closas, Montserrat
Publication Date
2019-08Journal Title
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN
1098-3600
Publisher
Wolters Kluwer Health
Volume
21
Issue
8
Pages
1708-1718
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Lee, A., Mavaddat, N., Wilcox, A. N., Cunningham, A., Carver, T., Hartley, S., Babb, C. L., et al. (2019). BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors.. Genetics in medicine : official journal of the American College of Medical Genetics, 21 (8), 1708-1718. https://doi.org/10.1038/s41436-018-0406-9
Abstract
Purpose: Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the BOADICEA risk model to incorporate the effects of Polygenic Risk Scores (PRS) and other risk factors (RFs).
Methods: BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2 and ATM; a PRS based on 313 SNPs explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs and mammographic density, while allowing for missing information.
Results: Among all factors considered, the predicted UK BC risk distribution is widest for the PRS, followed by mammographic density. The highest BC risk stratification is achieved when all genetic and lifestyle/hormonal/reproductive/anthropomorphic factors are considered jointly. With all factors, the predicted lifetime risks for women in the UK population vary from 2.8% for the 1st percentile to 30.6% for the 99th. 14.7% of women are predicted to have a lifetime risk of 17%-<30% (moderate risk according to NICE guidelines) and 1.1% a lifetime risk of 30% (high risk).
Conclusions: This comprehensive model should enable high levels of BC risk stratification in the general population and women with family history, and facilitate individualised, informed decision-making on prevention therapies and screening
Keywords
Humans, Breast Neoplasms, Ovarian Neoplasms, Genetic Predisposition to Disease, BRCA1 Protein, BRCA2 Protein, Risk Assessment, Risk Factors, Multifactorial Inheritance, Mutation, Polymorphism, Single Nucleotide, Female, Genetic Testing, Ataxia Telangiectasia Mutated Proteins, Checkpoint Kinase 2, Fanconi Anemia Complementation Group N Protein
Sponsorship
Cancer Research UK (20861)
Cancer Research UK (10119)
MRC (MR/P012930/1)
European Research Council (310018)
Wellcome Trust (203477/B/16/Z)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Cancer Research UK (CRUK-A16563)
Identifiers
External DOI: https://doi.org/10.1038/s41436-018-0406-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288440
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/