Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage
Document Type
Article
Publication Date
2-1-2025
Abstract
Background: A substantial portion of the genetic predisposition for breast cancer is explained by multiple common genetic variants of relatively small effect. A subset of these variants, which have been identified mostly in individuals of European (EUR) and Asian ancestries, have been combined to construct a polygenic risk score (PRS) to predict breast cancer risk, but the prediction accuracy of existing PRSs in Hispanic/Latinx individuals (H/L) remain relatively low. We assessed the performance of several existing PRS panels with and without addition of H/L-specific variants among self-reported H/L women.Methods: PRS performance was evaluated using multivariable logistic regression and the area under the ROC curve.Results: Both EUR and Asian PRSs performed worse in H/L samples compared with original reports. The best EUR PRS performed better than the best Asian PRS in pooled H/L samples. EUR PRSs had decreased performance with increasing Indigenous American (IA) ancestry, while Asian PRSs had increased performance with increasing IA ancestry. The addition of two H/L SNPs increased performance for all PRSs, most notably in the samples with high IA ancestry, and did not impact the performance of PRSs in individuals with lower IA ancestry.Conclusions: A single PRS that incorporates risk variants relevant to the multiple ancestral components of individuals from Latin America, instead of a set of ancestry-specific panels, could be used in clinical practice.Impact: The results highlight the importance of population-specific discovery and suggest a straightforward approach to integrate ancestry-specific variants into PRSs for clinical application.
Divisions
surgerydept
Funders
Placer Breast Cancer Endowed Chair, University of California Davis,United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI),California Precision Medicine Initiative Grant, Office of the California Governor,Universidad del Tolima, Colombia (10112) ; (520115),MINCIENCIAS, Colombia program "Becas Doctorales Nacionales" (528-2011) ; (647-2015),MINCIENCIAS, Colombia program "Formacion de Capital Humano de Alto Nivel para el Departamento de Tolima- 2016" (755-2016),L'OREAL-UNESCO-ICETEX-COLCIENCIAS, Colombia (3900917/2017),Coordinacion Nacional de Investigacion en Salud, Instituto Mexicano del Seguro Social, Mexico (FIS/IMSS/PROT/PRIO/13/027),Consejo Nacional de Ciencia y Tecnologia (CONACyT) (773),AACR Fellowship (21-40-69-ESTR),Heart, BrEast, and BrAin HeaLth Equity Research Program,GSK Oncology Ethnic Research Initiative,Towards Health Equity Oncology Grant, Gilead Sciences,Auburn Community Cancer Endowed Chair in Basic Research, U.S,United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) (R01-CA286650) ; (R01-CA273313) ; (R01-CA204797) ; (OPR18111) ; (19425) ; (5D43CA260869-01)
Publication Title
Cancer Epidemiology Biomarkers & Prevention
Volume
34
Issue
2
Publisher
American Association for Cancer Research
Publisher Location
615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA