Assessing the Risk Stratification of Breast Cancer Polygenic Risk Scores in a Brazilian Cohort

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Barreiro, Rodrigo A. S. ; de Almeida, Tatiana F. ; Gomes, Catarina ; Monfardini, Frederico ; de Farias, Allysson A. ; Tunes, Gabriela C. ; de Souza, Gabriel M. ; Duim, Etienne ; de Sa Correia, Jaqueline ; Coelho, Antonio V. Campos ; Caraciolo, Marcel P. ; Duarte, Yeda A. Oliveira ; Zatz, Mayana ; Amaro, Edson ; Oliveira, Joao B. ; Bitarello, Barbara D. ; Brentani, Helena ; Naslavsky, Michel S.

• Document type: Journal article
• Source: JOURNAL OF MOLECULAR DIAGNOSTICS; v. 26, n. 9, p. 7-pg., 2024-08-23.

Abstract

Polygenic risk scores (PRSs) for breast cancer have a clear clinical utility in risk prediction. PRS transferability across populations and ancestry groups is hampered by population-specific factors, ultimately leading to differences in variant effects, such as linkage disequilibrium and differences in variant frequency (allele frequency differences). Thus, locally sourced population-based phenotypic and genomic data sets are essential to assess the validity of PRSs derived from signals detected across populations. This study assesses the transferability of a breast cancer PRS composed of 313 risk variants (313-PRS) in a Brazilian trihybrid admixed ancestries (European, African, and Native American) wholegenome sequenced cohort, the Rare Genomes Project. 313-PRS was computed in the Rare Genomes Project (n = 853) using the UK Biobank (UKBB; n = 264,307) as reference. The Brazilian cohorts have a high European ancestry (EA) component, with allele frequency differences and to a lesser extent linkage disequilibrium patterns similar to those found in EA populations. The 313-PRS distribution was found to be inflated when compared with that of the UKBB, leading to potential overestimation of PRSbased risk if EA is taken as a standard. However, case controls lead to equivalent predictive power when compared with UKBB-EA samples with area under the receiver operating characteristic curve values of 0.66 to 0.62 compared with 0.63 for UKBB. (J Mol Diagn 2024, 26: 825-831; https://doi.org/10.1016/ j.jmoldx.2024.06.002) (AU)

• FAPESP's process: 18/18560-6 - Data integration to identify biological markers of neurodevelopmental disorders
• Grantee: Helena Paula Brentani
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/50931-3 - Aging and genetic disorders: genomics and metagenomics
• Grantee: Mayana Zatz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/16376-3 - Determination of polygenic risk to characterize exposure to gestational stress
• Grantee: Catarina dos Santos Gomes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 14/50649-6 - SABE study: a longitudinal study of multiple cohorts on the elderly life and health conditions in the municipality of São Paulo - cohort 2015
• Grantee: Yeda Aparecida de Oliveira Duarte
• Support Opportunities: Research Projects - Thematic Grants