Polygenic risk and rare variant gene clustering enhance cancer risk stratification for breast and prostate cancers.

ABSTRACT: Polygenic risk score (PRS) and rare monogenic variant screening are valuable tools for predicting cancer risk and identifying individuals at high risk. Integrating both common and rare genetic variants is crucial for accurate risk assessment. However, estimating the impacts of rare variants on cancer and combining them with PRS remains challenging. Here, we analyze 454,711 exome sequencing and 487,409 array UK Biobank samples, focusing on breast and prostate cancers. We introduce an expanded PRS (EPRS) approach, yielding a systematic model for more effective risk stratification. By prioritizing and clustering genes with cancer-specific rare variants based on odds ratios and population-attributable fraction, we refine risk stratification by combining both monogenic and polygenic effects. In

SUBMITTER: Kang JH 

PROVIDER: S-EPMC11464688 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature