Polygenic Risk Score Predicts Modified Risk in BRCA1 Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients

Author:

Berga-Švītiņa Egija12ORCID,Maksimenko Jeļena23ORCID,Miklaševičs Edvīns24,Fischer Krista56,Vilne Baiba1ORCID,Mägi Reedik5

Affiliation:

1. Bioinformatics Lab, Rīga Stradiņš University, Dzirciema Street 16, LV-1007 Riga, Latvia

2. Institute of Oncology, Rīga Stradiņš University, Pilsoņu Street 13, Block 13, LV-1002 Riga, Latvia

3. Pauls Stradiņš Clinical University Hospital, Pilsoņu Street 13, LV-1002 Riga, Latvia

4. Department of Biology and Microbiology, Rīga Stradiņš University, LV-1007 Riga, Latvia

5. Institute of Genomics, University of Tartu, Riia 23b, 51010 Tartu, Estonia

6. Institute of Mathematics and Statistics, University of Tartu, Narva mnt 18, 51009 Tartu, Estonia

Abstract

The aim of this study was to assess the power of the polygenic risk score (PRS) in estimating the overall genetic risk of women carrying germline BRCA1 pathogenic variants (PVs) c.4035del or c.5266dup to develop breast (BC) or ovarian cancer (OC) due to additional genetic variations. In this study, PRSs previously developed from two joint models using summary statistics of age-at-onset (BayesW model) and case–control data (BayesRR-RC model) from a genome-wide association analysis (GWAS) were applied to 406 germline BRCA1 PV (c.4035del or c.5266dup) carriers affected by BC or OC, compared with unaffected individuals. A binomial logistic regression model was used to assess the association of PRS with BC or OC development risk. We observed that the best-fitting BayesW PRS model effectively predicted the individual’s BC risk (OR = 1.37; 95% CI = 1.03–1.81, p = 0.02905 with AUC = 0.759). However, none of the applied PRS models was a good predictor of OC risk. The best-fitted PRS model (BayesW) contributed to assessing the risk of developing BC for germline BRCA1 PV (c.4035del or c.5266dup) carriers and may facilitate more precise and timely patient stratification and decision-making to improve the current BC treatment or even prevention strategies.

Funder

European Social Fund and Latvian state budget

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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