A Breast Cancer Polygenic Risk Score Validation in 15,490 Brazilians Using Exome Sequencing

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 ev...

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Main Authors: Flávia Eichemberger Rius, Rodrigo Santa Cruz Guindalini, Danilo Viana, Júlia Salomão, Laila Gallo, Renata Freitas, Cláudia Bertolacini, Lucas Taniguti, Danilo Imparato, Flávia Antunes, Gabriel Sousa, Renan Achjian, Eric Fukuyama, Cleandra Gregório, Iuri Ventura, Juliana Gomes, Nathália Taniguti, Simone Maistro, José Eduardo Krieger, Yonglan Zheng, Dezheng Huo, Olufunmilayo I. Olopade, Maria Aparecida Azevedo Koike Folgueira, David Schlesinger
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Diagnostics
Subjects:
polygenic risk score (PRS)
breast cancer
admixed population
cancer genetics
next-generation sequencing (NGS)
precision medicine
Online Access:https://www.mdpi.com/2075-4418/15/9/1098
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Summary:<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.
ISSN:2075-4418

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