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Evaluation of multiple breast cancer polygenic risk score panels in women of Latin American heritage

2024; American Association for Cancer Research; Linguagem: Inglês

10.1158/1055-9965.epi-24-1247

1538-7755

Xiaosong Huang, Paul C. Lott, Donglei Hu, Valentina A. Zavala, Zoeb N. Jamal, Tatiana Vidaurre, Sandro Casavilca‐Zambrano, Jeannie Navarro Vásquez, Carlos A. Castañeda, Guillermo Valencia, Zaida Morante, Mónica Calderón, Julio E. Abugattas, Hugo Fuentes, Ruddy Liendo-Picoaga, José M. Cotrina, Silvia P. Neciosup, Patricia Rioja, Luis A. Salinas, Marco Gálvez-Niño, Scott Huntsman, Sixto E. Sánchez, Michelle A. Williams, Bizu Gelaye, Ana P. Estrada-Florez, Guadalupe Polanco‐Echeverry, Magdalena Echeverry, Alejandro Vélez Hoyos, Jenny A. Carmona-Valencia, Mábel Bohórquez, Javier Torres, Miguel Cruz, Weang-Kee Ho, Soo‐Hwang Teo, Mei-Chee Tai, Esther M. John, Christopher A. Haiman, David V. Conti, Fei Chen, Gabriela Torres-Mejı́a, Lawrence H. Kushi, Susan L. Neuhausen, Elad Ziv, Luis G. Carvajal‐Carmona, Laura Fejerman,

Nutrition, Genetics, and Disease

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 and Asian ancestry, 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 receiver operating characteristic curve (AUC). Results: Both European and Asian PRSs performed worse in H/L samples compared to original reports. The best European PRS performed better than the best Asian PRS in pooled H/L samples. European PRSs had decreased performance with increasing Indigenous American (IA) ancestry while Asian PRSs had increased performance with increasing IA ancestry. The addition of 2 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: Results highlight the importance of population-specific discovery and suggest a straightforward approach to integrate ancestry specific variants into PRS for clinical application.