Validation of the BOADICEA model and a 313-variant polygenic risk score for breast cancer risk prediction in a Dutch prospective cohort

Abstract: Purpose: We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort, using a polygenic risk score (PRS) based on 313 breast cancer (BC)–associated variants (PRS313) and other, nongenetic risk factors. Methods: Since 1989, 6522 women without BC aged 45 or older of European descent have been included in the Rotterdam Study. The PRS313 was calculated per 1 SD in controls from the Breast Cancer Association Consortium (BCAC). Cox regression analysis was performed... Mehr ...

Verfasser: Lakeman, Inge M. M.
Rodríguez-Girondo, Mar
Lee, Andrew
Ruiter, Rikje
Stricker, Bruno H.
Wijnant, Sara R. A.
Kavousi, Maryam
Antoniou, Antonis C.
Schmidt, Marjanka K.
Uitterlinden, André G.
van Rooij, Jeroen
Devilee, Peter
Dokumenttyp: Artikel
Erscheinungsdatum: 2020
Verlag/Hrsg.: Nature Publishing Group US
Schlagwörter: Article / breast cancer / polygenic risk score / prospective cohort / risk assessment
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27061813
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://doi.org/10.17863/CAM.59312

Abstract: Purpose: We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort, using a polygenic risk score (PRS) based on 313 breast cancer (BC)–associated variants (PRS313) and other, nongenetic risk factors. Methods: Since 1989, 6522 women without BC aged 45 or older of European descent have been included in the Rotterdam Study. The PRS313 was calculated per 1 SD in controls from the Breast Cancer Association Consortium (BCAC). Cox regression analysis was performed to estimate the association between the PRS313 and incident BC risk. Cumulative 10-year risks were calculated with BOADICEA including different sets of variables (age, risk factors and PRS313). C-statistics were used to evaluate discriminative ability. Results: In total, 320 women developed BC. The PRS313 was significantly associated with BC (hazard ratio [HR] per SD of 1.56, 95% confidence interval [CI] [1.40–1.73]). Using 10-year risk estimates including age and the PRS313, other risk factors improved the discriminatory ability of the BOADICEA model marginally, from a C-statistic of 0.636 to 0.653. Conclusions: The effect size of the PRS313 is highly reproducible in the Dutch population. Our results validate the BOADICEA v5 model for BC risk assessment in the Dutch general population.