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Updated: Jun 25, 2026

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors
Published on: February 28, 2021
The Clinical Application of Refined Risk Estimates Study in BRCA1 and BRCA2 Pathogenic Variant Carriers: A Randomized
Leigha Senter1, Shelly Hovick2, Rachel Notestine3
1Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Abstract:
Individuals with germline BRCA1 or BRCA2 pathogenic variants (PV) may struggle with risk management decision-making. Advancements in technology could provide more specific risk information to patients, but the impact of this information is unknown. The Clinical Application of Refined Risk Estimates Study is a two-arm randomized controlled trial in women with a BRCA1/BRCA2 PV. The primary objective was to determine whether genotype-informed personalized cancer risk estimates (GRE) compared with standard lifetime cancer risk estimates (SRE) decreased decisional conflict related to cancer risk management decision-making. Women were recruited following the disclosure of their PV results. Participants completed a baseline survey and were randomized 1:1 to receive a GRE or SRE. After receiving their results, participants completed a follow-up survey. Likert and continuous data measures were analyzed using linear regression. There were no differences in decisional conflict between study arms at follow-up. However, individuals in the SRE arm showed an increased need for personal structure compared with those in the GRE arm (P = 0.02). Compared with baseline, individuals within the SRE arm showed decreased decisional conflict (P = 0.003) and increased perceived stress (P = 0.02) at follow-up. A more personalized cancer risk estimate did not decrease decisional conflict in women with BRCA1/BRCA2 PVs. Future studies will determine whether a GRE affects actual decision-making behaviors.
Prevention Relevance:
Women with a germline PV in BRCA1 or BRCA2 have significantly elevated risks of developing breast and ovarian cancers. This randomized controlled trial evaluates the impact of polygenic risk scores on decisional conflict related to breast and ovarian cancer prevention and risk management in those with BRCA1/BRCA2 PVs.
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