Association of high and moderate penetrance monogenic variants, polygenic risk, and family history with breast cancer in an ancestrally diverse population.

Diverse biobank (30,223 individuals): OR assessment of high/moderate penetrance variants × PRS × family history for breast cancer

In an ancestrally diverse biobank of 30,223 individuals (including 15,919 unrelated women), pathogenic variants in 14 genes are associated with increased breast cancer risk with or without family history (OR 6.8 and 11.8 respectively for high penetrance genes). PRS significantly augments risk associated with moderate penetrance variants. Data are stratified by ancestry, highlighting the importance of diversity in risk score construction.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Integrating PRS + monogenic variants + family history is the central challenge for breast cancer risk stratification in oncogenetics over the next decade. This diverse population study confirms that PRS amplifies risk conferred by moderate penetrance genes (CHEK2, ATM, PALB2) — an argument for systematically integrating PRS into breast oncogenetics consultations.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 0/1 → Total: 6/10