Polygenic risk score for breast cancer risk prediction in Asian BRCA1 and BRCA2 pathogenic variants carriers

Abstract

<p>Polygenic risk scores (PRS) have been shown to be predictive of breast cancer (BC) risk in European <em>BRCA1</em> and <em>BRCA2</em> pathogenic variant (PV) carriers, but their utility in Asian populations has not been evaluated. In this study, we evaluated the association of two breast cancer PRS developed for the East Asian general population and three versions of a PRS developed for the European general population in 604 <em>BRCA1</em> (390 affected by breast cancer) and 785 <em>BRCA2</em> (552 affected by breast cancer) PV female carriers of Asian ancestry. Only the Asian-based PRS, constructed using approximately 1 million single-nucleotide variations (SNVs), showed a significant association with breast cancer risk (Hazard Ratio per standard deviation (95% Confidence Interval) is 1.47 (1.10–1.95) for <em>BRCA1</em> and 1.43 (1.04–1.95) for <em>BRCA2</em>). Incorporating this PRS into risk prediction models may improve cancer risk assessment among PV carriers of Asian ancestry.<br></p>