Abstract PO2-08-03: Developing a polygenic risk score for precision prevention of estrogen receptor-positive (ER+)/HER2- breast cancer in Brazilian women
Authors: Marina Candido Visontai Cormedi, Álison Luís Eburnêo Pereira, Fernanda Borchers Coeli-Lacchini, Sabrina Baroni, Lívia Mara Torres Bueno, Evelyn Ayumi Onga, Victor Girelli Piloto De Oliveira, Fabiana De Oliveira Buono, Aline Fares, Tatiana Strava Correa, Iasmin Alves Chirichela, Fernanda Peria, Romulado Barroso-Sousa, Rodrigo Santa Cruz Guindalini, Taisa Manuela Bonfim Machado Lopes, Rosimeire Aparecida Roela, Maria Aparecida Azevedo Koike Folgueira, Daniel Guimarães Tiezzi, Leandro Machado Colli, Liane Rapatoni
Journal: Cancer Research (2024)

Abstract Polygenic risk scores (PRS) quantify the genetic risk of diseases based on risk alleles in genomic loci identified in genome-wide association studies (GWAS). As individuals of European ancestry are overrepresented in GWAS, PRS performance may vary in individuals of different ancestries. Brazil is the largest and most populated country in Latin America, with around 43% of admixed individuals, and data on breast cancer PRS performance for this population is lacking. We aimed to evaluate the performance of a breast cancer PRS with 313 SNPs generated with Europeans in Brazilian population. In this case-control study, we expect to include 1000 women age &amp;gt;= 18 years old with current or previous diagnosis of ER+/HER2- breast cancer. Germline DNA samples are genotyped with Illumina Infinium Global Screening Array-24 v3.0 chip. Controls are healthy woman previously genotyped with Global Screening Array-24 v1.0 chip. We selected the 313 SNPs PRS for ER+/HER2- breast cancer from PGS Catalog for evaluation. Quality control, imputation, PRS calculation and statistical analysis were performed in PLINK v2.0, Michigan server, PGS Catalog and R, respectively. We present the preliminary results for 1347 women (504 cases and 843 controls) included until March of 2023. After quality control and imputation, we calculated PRS for 1212 subjects (475 cases and 737 controls). Out of 313 SNPs, 211 were validated in our samples. For ER+/HER2- breast cancer, the odds ratio per SD of the 211-variant PRS (PRS211) was 1.363 (95% confidence interval [CI]: 1.211 to 1.537). Compared with women with average risk (40th-60th PRS percentile), women in the top 10% of PRS211 had a 1.623-fold increased risk (95% CI: 1.047 to 2.522). The area under the receiver operating characteristic curve of 0.581. Our preliminary results indicate that a PRS derived from European-ancestry population correlates with ER+/HER2- breast cancer in admixed Brazilian population, although with attenuated performance. Further work is needed to better characterize PRS risk stratification in admixed populations. Citation Format: Marina Candido Visontai Cormedi, Álison Luís Eburnêo Pereira, Fernanda Borchers Coeli-Lacchini, Sabrina Baroni, Lívia Mara Torres Bueno, Evelyn Ayumi Onga, Victor Girelli Piloto De Oliveira, Fabiana De Oliveira Buono, Aline Fares, Tatiana Strava Correa, Iasmin Alves Chirichela, Fernanda Peria, Romulado Barroso-Sousa, Rodrigo Santa Cruz Guindalini, Taisa Manuela Bonfim Machado Lopes, Rosimeire Aparecida Roela, Maria Aparecida Azevedo Koike Folgueira, Daniel Guimarães Tiezzi, Leandro Machado Colli, Liane Rapatoni. Developing a polygenic risk score for precision prevention of estrogen receptor-positive (ER+)/HER2- breast cancer in Brazilian women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-03.