A Breast Cancer Polygenic Risk Score Validation in 15,490 Brazilians Using Exome Sequencing
<b>Background/Objectives</b>: Brazil has a highly admixed population. Polygenic risk scores (PRSs) have mostly been developed from European population studies, and their application to other populations is challenging. To assess the use of PRS for breast cancer (BC) risk in Brazil, we evaluated four PRSs in the Brazilian population. <b>Methods:</b> We analyzed a Brazilian cohort composed of 6206 women with a history of breast cancer and 8878 unphenotyped adults as controls. Genomic variants were imputed from exomes, and scores were calculated for all samples. <b>Results:</b> After individuals with known pathogenic or likely pathogenic variants in <i>BRCA1</i>, <i>BRCA2</i>, <i>PALB2</i>, <i>PTEN</i>, or <i>TP53</i> genes, and first-degree relatives of the probands were excluded, 5598 cases and 8767 controls remained. Four PRS models were compared, and PRS<sub>3820</sub> achieved the best performance, with an odds ratio (OR) of 1.43 per standard deviation increase (<i>p</i> value < 0.001) and an OR of 1.88 (<i>p</i> value < 0.001) for the top decile. PRS<sub>3820</sub> also performed well for different ancestry groups: East Asian majority (OR 1.59, <i>p</i> value 0.004), Non-European majority (OR 1.45, <i>p</i> value < 0.001), and European majority (OR 1.43, <i>p</i> value < 0.001). <b>Conclusions:</b> Among the different PRSs, PRS<sub>313</sub> and PRS<sub>3820</sub> could be validated in our Brazilian cohort, with the latter exhibiting the best performance. While further clinical studies are necessary to guide clinical practice, this work represents an important step toward improving BC precision medicine in Brazil.
Authors
- Flávia E. Rius (ORCID: https://orcid.org/0000-0002-5946-1165)
- Júlia Salomão
- David Schlesinger
- Danilo Oliveira Imparato (ORCID: https://orcid.org/0000-0001-6979-4951)
- Dezheng Huo (ORCID: https://orcid.org/0000-0002-4041-1678)
- Maria Aparecida Azevedo Koike Folgueira (ORCID: https://orcid.org/0000-0001-9269-8052)
- Cleandra Gregório (ORCID: https://orcid.org/0000-0002-6476-219X)
- Flávia Antunes
- Renata Freitas (ORCID: https://orcid.org/0000-0002-0123-7232)
- Renan W. Achjian (ORCID: https://orcid.org/0000-0002-1703-4085)
- Olufunmilayo I. Olopade (ORCID: https://orcid.org/0000-0002-9936-1599)
- Claudia Danielli Pereira Bertolacini
- Rodrigo Santa Cruz Guindalini (ORCID: https://orcid.org/0000-0002-5198-8966)
- Lucas Mitsuo Taniguti (ORCID: https://orcid.org/0000-0002-2682-7343)
- Simone Maistro (ORCID: https://orcid.org/0000-0002-0937-2391)
- José Eduardo Krieger (ORCID: https://orcid.org/0000-0001-5464-1792)
- Yonglan Zheng (ORCID: https://orcid.org/0000-0001-6597-7072)
- Nathália Taniguti
- Gabriel Gomes de Sousa (ORCID: https://orcid.org/0000-0002-5272-8592)
- Juliana de Assis Silva Gomes (ORCID: https://orcid.org/0000-0002-8332-2907)
- Laila Gallo
- Eric Fukuyama
- Iuri Ventura
- Danilo Viana (ORCID: https://orcid.org/0009-0004-1740-915X)
Institutions
- Chicago Department of Public Health (US)
- Universidade de São Paulo (BR)
- University of Chicago (US)
- University of Chicago Medical Center (US)
- Instituto do Câncer do Estado de São Paulo (BR)
- D’Or Institute for Research and Education (BR)
- Mendelics (BR)
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- Cancer Genetics (United States) (US)
Publication Details
- Journal
- Diagnostics
- Published
- 2025-04-25
- DOI
- https://doi.org/10.3390/diagnostics15091098
- Citations
- 2
- Primary Topic
- BRCA gene mutations in cancer
- Type
- article
- Field-Weighted Citation Impact
- 3.63
Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico