Evaluation of Multiple Breast Cancer Polygenic Risk Score Panels in Women of Latin American Heritage

作者：Xiaosong Huang, Paul C. Lott, Donglei Hu, Valentina A. Zavala, Zoeb N. Jamal, Tatiana Vidaurre, Sandro Casavilca‐Zambrano, Jeannie Navarro Vásquez, Carlos Arturo Castañeda, Guillermo Valencia, Zaida Morante, Mónica J. Calderón, Julio E. Abugattas, Hugo Alejandro Fuentes, Ruddy Liendo-Picoaga, Jose Manuel Cotrina, Silvia P. Neciosup, Patricia Rioja, Luis A. Salinas, Marco Gálvez-Niño, Scott Huntsman, Sixto E. Sánchez, Michelle Anne Williams, Bizu Gelaye, Ana Patricia Estrada-Florez, Guadalupe M. 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 · 发表于：Cancer Epidemiology Biomarkers & Prevention · 年份：2024 · DOI：10.1158/1055-9965.epi-24-1247 · 被引用次数：6 · 研究领域：BRCA gene mutations in cancer、Genetic Associations and Epidemiology、Breast Cancer Treatment Studies

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...