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  1. Moreira DC, Rajagopal R, Navarro-Martin Del Campo RM, Polanco AC, Alcasabas AP, Arredondo-Navarro LA, et al.
    JCO Glob Oncol, 2020 04;6:583-584.
    PMID: 32293939 DOI: 10.1200/GO.20.00047
  2. Huang X, Lott PC, Hu D, Zavala VA, Jamal ZN, Vidaurre T, et al.
    PMID: 39625644 DOI: 10.1158/1055-9965.EPI-24-1247
    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.

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