Show simple item record

dc.contributor.authorLee, Andrew
dc.contributor.authorMavaddat, Nasim
dc.contributor.authorCunningham, Alex
dc.contributor.authorCarver, Tim
dc.contributor.authorFicorella, Lorenzo
dc.contributor.authorArcher, Stephanie
dc.contributor.authorWalter, Fiona M
dc.contributor.authorTischkowitz, Marc
dc.contributor.authorRoberts, Jonathan
dc.contributor.authorUsher-Smith, Juliet
dc.contributor.authorSimard, Jacques
dc.contributor.authorSchmidt, Marjanka K
dc.contributor.authorDevilee, Peter
dc.contributor.authorZadnik, Vesna
dc.contributor.authorJürgens, Hannes
dc.contributor.authorMouret-Fourme, Emmanuelle
dc.contributor.authorDe Pauw, Antoine
dc.contributor.authorRookus, Matti
dc.contributor.authorMooij, Thea M
dc.contributor.authorPharoah, Paul Pd
dc.contributor.authorEaston, Douglas F
dc.contributor.authorAntoniou, Antonis C
dc.description.abstractBACKGROUND: BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool ( provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors. METHODS: BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult height as continuous. RESULTS: BARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34%-44% of these carriers would be reclassified to the near-population and 15%-22% to the high-risk categories based on the UK National Institute for Health and Care Excellence guidelines. Under the EOC multifactorial model, 62%, 35% and 3% of PALB2 carriers have lifetime EOC risks of <5%, 5%-10% and >10%, respectively. Including height as continuous, increased the breast cancer relative risk variance from 0.002 to 0.010. CONCLUSIONS: These extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.
dc.rightsAttribution 4.0 International
dc.subjectgenetic counseling
dc.subjectGenetic Predisposition to Disease
dc.subjectBRCA1 Protein
dc.subjectOvarian Neoplasms
dc.subjectBreast Neoplasms
dc.subjectCarcinoma, Ovarian Epithelial
dc.subjectRisk Factors
dc.subjectTumor Suppressor Proteins
dc.subjectUbiquitin-Protein Ligases
dc.subjectDNA-Binding Proteins
dc.titleEnhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1 updates to tumour pathology and cancer incidence.
dc.publisher.departmentDepartment of Public Health And Primary Care, Cancer Genetic Epidemiology
prism.publicationNameJ Med Genet
dc.contributor.orcidLee, Andrew [0000-0003-0677-0252]
dc.contributor.orcidDevilee, Peter [0000-0002-8023-2009]
dc.contributor.orcidPharoah, Paul Pd [0000-0001-8494-732X]
dc.contributor.orcidAntoniou, Antonis C [0000-0001-9223-3116]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (20861)
pubs.funder-project-idCancer Research UK (C12292/A31369)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (634935)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (633784)
pubs.funder-project-idNational Institute for Health Research (IS-BRC-1215-20014)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International