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

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 estima... Mehr ...

Verfasser: Lakeman, I.M.M. (Inge M. M.)
Rodríguez-Girondo, M. (Mar)
Lee, A. (Andrew)
Ruiter, T.R. (Rikje)
Stricker, B.H.Ch. (Bruno)
Wijnant, S.R.A. (Sara R. A.)
Kavousi, M. (Maryam)
Antoniou, A.C. (Antonis C.)
Schmidt, M.K. (Marjanka)
Uitterlinden, A.G. (André)
Rooij, J.G.J. (Jeroen) van
Devilee, P. (Peter)
Dokumenttyp: Artikel
Erscheinungsdatum: 2020
Schlagwörter: breast cancer / polygenic risk score / prospective cohort / risk assessment
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29035291
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://repub.eur.nl/pub/128748

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.