British journal of cancer · 2024
Validation of the BOADICEA model for epithelial tubo-ovarian cancer risk prediction in UK Biobank.
СтатьяВалидационное исследованиеНазвание и аннотация: Перевод в очереди
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Yang Xin, Wu Yujia, Ficorella Lorenzo, Wilcox Naomi, Dennis Joe, Tyrer Jonathan, Carver Tim, Pashayan Nora, Tischkowitz Marc, Pharoah Paul D P, Easton Douglas F, Antoniou Antonis C
Аннотация
BACKGROUND: The 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.
METHODS: We 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).
RESULTS: Discriminative 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.
DISCUSSION: BOADICEA, implemented in CanRisk ( www.canrisk.org ), provides valid 10-year EOC risks and can facilitate clinical decision-making in EOC risk management.
METHODS: We 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).
RESULTS: Discriminative 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.
DISCUSSION: BOADICEA, implemented in CanRisk ( www.canrisk.org ), provides valid 10-year EOC risks and can facilitate clinical decision-making in EOC risk management.
Предметные рубрики MeSH
HumansFemaleMiddle AgedUnited KingdomCarcinoma, Ovarian EpithelialBRCA2 ProteinAgedOvarian NeoplasmsBiological Specimen BanksBRCA1 ProteinGenetic Predisposition to DiseaseRisk FactorsRisk AssessmentDNA-Binding ProteinsFanconi Anemia Complementation Group N ProteinAdultPolymorphism, Single NucleotideFallopian Tube NeoplasmsUK BiobankRNA HelicasesFanconi Anemia Complementation Group Proteins