| Title: | Validation of the BOADICEA model for epithelial tubo-ovarian cancer risk prediction in UK Biobank |
| Journal: | British Journal of Cancer |
| Published: | 18 Sep 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39294438/ |
| DOI: | https://doi.org/10.1038/s41416-024-02851-z |
Publication 13468
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Abstract
BackgroundThe clinical validity of the multifactorial BOADICEA model for epithelial tubo-ovarian cancer (EOC) risk prediction has not been assessed in a large sample size or over a longer term.MethodsWe evaluated the model discrimination and calibration in the UK Biobank cohort comprising 199,429 women (733 incident EOCs) of European ancestry without previous cancer history. We predicted 10-year EOC risk incorporating data on questionnaire-based risk factors (QRFs), family history, a 36-SNP polygenic risk score and pathogenic variants (PV) in six EOC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1 and PALB2).ResultsDiscriminative ability was maximised under the multifactorial model that included all risk factors (AUC = 0.68, 95% CI: 0.66-0.70). This model was well calibrated in deciles of predicted risk with calibration slope=0.99 (95% CI: 0.98-1.01). Discriminative ability was similar in women younger or older than 60 years. The AUC was higher when analyses were restricted to PV carriers (0.76, 95% CI: 0.69-0.82). Using relative risk (RR) thresholds, the full model classified 97.7%, 1.7%, 0.4% and 0.2% women in the RR < 2.0, 2.0 ≤ RR < 2.9, 2.9 ≤ RR < 6.0 and RR ≥ 6.0 categories, respectively, identifying 9.1 of incident EOC among those with RR ≥ 2.0.DiscussionBOADICEA, implemented in CanRisk (www.canrisk.org), provides valid 10-year EOC risks and can facilitate clinical decision-making in EOC risk management.</p>
21 Keywords
- Adult
- Aged
- BRCA1 Protein
- BRCA2 Protein
- Biological Specimen Banks
- Carcinoma, Ovarian Epithelial
- DNA-Binding Proteins
- Fallopian Tube Neoplasms
- Fanconi Anemia Complementation Group N Protein
- Fanconi Anemia Complementation Group Proteins
- Female
- Genetic Predisposition to Disease
- Humans
- Middle Aged
- Ovarian Neoplasms
- Polymorphism, Single Nucleotide
- RNA Helicases
- Risk Assessment
- Risk Factors
- UK Biobank
- United Kingdom
12 Authors
- Xin Yang
- Yujia Wu
- Lorenzo Ficorella
- Naomi Wilcox
- Joe Dennis
- Jonathan Tyrer
- Tim Carver
- Nora Pashayan
- Marc Tischkowitz
- Paul D. P. Pharoah
- Douglas F. Easton
- Antonis C. Antoniou
1 Application
| Application ID | Title |
|---|---|
| 28126 | Validating risk prediction models for common hormonal cancers |
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