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Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage
- Huang, Xiaosong;
- Lott, Paul C;
- Hu, Donglei;
- Zavala, Valentina A;
- Jamal, Zoeb N;
- Vidaurre, Tatiana;
- Casavilca-Zambrano, Sandro;
- Vásquez, Jeannie Navarro;
- Castañeda, Carlos A;
- Valencia, Guillermo;
- Morante, Zaida;
- Calderón, Mónica;
- Abugattas, Julio E;
- Fuentes, Hugo A;
- Liendo-Picoaga, Ruddy;
- Cotrina, Jose M;
- Neciosup, Silvia P;
- Viera, Patricia Rioja;
- Salinas, Luis A;
- Galvez-Nino, Marco;
- Huntsman, Scott;
- Sanchez, Sixto E;
- Williams, Michelle A;
- Gelaye, Bizu;
- Estrada-Florez, Ana P;
- Polanco-Echeverry, Guadalupe;
- Echeverry, Magdalena;
- Velez, Alejandro;
- Carmona-Valencia, Jenny A;
- Bohorquez-Lozano, Mabel E;
- Torres, Javier;
- Cruz, Miguel;
- Ho, Weang-Kee;
- Teo, Soo Hwang;
- Tai, Mei Chee;
- John, Esther M;
- Haiman, Christopher A;
- Conti, David V;
- Chen, Fei;
- Torres-Mejía, Gabriela;
- Kushi, Lawrence H;
- Neuhausen, Susan L;
- Ziv, Elad;
- Carvajal-Carmona, Luis G;
- Consortium, for the COLUMBUS;
- Fejerman, Laura
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.