Polygenic Risk Score Predicts Modified Risk in <i>BRCA1</i> Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients
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 <i>BRCA1</i> pathogenic variants (PVs) c.4035del or c.5266dup to develop breast (BC) or ovarian cancer (OC) due to additional genetic variatio...
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| Format: | Article |
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MDPI AG
2023-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/11/2957 |
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| author | Egija Berga-Švītiņa Jeļena Maksimenko Edvīns Miklaševičs Krista Fischer Baiba Vilne Reedik Mägi |
| author_facet | Egija Berga-Švītiņa Jeļena Maksimenko Edvīns Miklaševičs Krista Fischer Baiba Vilne Reedik Mägi |
| author_sort | Egija Berga-Švītiņa |
| collection | DOAJ |
| description | 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 <i>BRCA1</i> 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 <i>BRCA1</i> 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, <i>p</i> = 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 <i>BRCA1</i> 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. |
| first_indexed | 2024-03-11T03:10:10Z |
| format | Article |
| id | doaj.art-0bd521f81ace473dbedab0adb26a9ae2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:10:10Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0bd521f81ace473dbedab0adb26a9ae22023-11-18T07:38:49ZengMDPI AGCancers2072-66942023-05-011511295710.3390/cancers15112957Polygenic Risk Score Predicts Modified Risk in <i>BRCA1</i> Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer PatientsEgija Berga-Švītiņa0Jeļena Maksimenko1Edvīns Miklaševičs2Krista Fischer3Baiba Vilne4Reedik Mägi5Bioinformatics Lab, Rīga Stradiņš University, Dzirciema Street 16, LV-1007 Riga, LatviaInstitute of Oncology, Rīga Stradiņš University, Pilsoņu Street 13, Block 13, LV-1002 Riga, LatviaInstitute of Oncology, Rīga Stradiņš University, Pilsoņu Street 13, Block 13, LV-1002 Riga, LatviaInstitute of Genomics, University of Tartu, Riia 23b, 51010 Tartu, EstoniaBioinformatics Lab, Rīga Stradiņš University, Dzirciema Street 16, LV-1007 Riga, LatviaInstitute of Genomics, University of Tartu, Riia 23b, 51010 Tartu, EstoniaThe 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 <i>BRCA1</i> 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 <i>BRCA1</i> 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, <i>p</i> = 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 <i>BRCA1</i> 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.https://www.mdpi.com/2072-6694/15/11/2957polygenic risk score (PRS)breast cancerovarian cancer<i>BRCA1</i> pathogenic variant carriers |
| spellingShingle | Egija Berga-Švītiņa Jeļena Maksimenko Edvīns Miklaševičs Krista Fischer Baiba Vilne Reedik Mägi Polygenic Risk Score Predicts Modified Risk in <i>BRCA1</i> Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients Cancers polygenic risk score (PRS) breast cancer ovarian cancer <i>BRCA1</i> pathogenic variant carriers |
| title | Polygenic Risk Score Predicts Modified Risk in <i>BRCA1</i> Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients |
| title_full | Polygenic Risk Score Predicts Modified Risk in <i>BRCA1</i> Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients |
| title_fullStr | Polygenic Risk Score Predicts Modified Risk in <i>BRCA1</i> Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients |
| title_full_unstemmed | Polygenic Risk Score Predicts Modified Risk in <i>BRCA1</i> Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients |
| title_short | Polygenic Risk Score Predicts Modified Risk in <i>BRCA1</i> Pathogenic Variant c.4035del and c.5266dup Carriers in Breast Cancer Patients |
| title_sort | polygenic risk score predicts modified risk in i brca1 i pathogenic variant c 4035del and c 5266dup carriers in breast cancer patients |
| topic | polygenic risk score (PRS) breast cancer ovarian cancer <i>BRCA1</i> pathogenic variant carriers |
| url | https://www.mdpi.com/2072-6694/15/11/2957 |
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