Improving Consistency in Colorectal Cancer Genetic Risk Assessment and Return of Results Through an Integrated Polygenic Risk Score

Background: Published colorectal cancer (CRC) polygenic risk scores (PRS) may demonstrate similar population-level predictive performance but often assign substantially different risk classifications to the same individuals. Such discordance presents challenges for clinical implementation and return of results (RoR). Methods: We developed a stable PRS for CRC (stPRS-CRC) by integrating 28 published PRS using PRSmix in the All of Us (AoU) development cohort (n=321,703). Performance was evaluated in a held-out AoU validation cohort (n=80,423) and independently validated in the Genomic Health Ini

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