Polygenic risk score (PRS) and its potential for breast cancer risk stratification

Czech version

Authors: M. Hovhannisyan ¹; P. Kleiblová ^1,2; P. Nehasil ^1,3,4; J. Soukupová ¹; P. Zemánková ^1,3; Z. Kleibl ^1,3; M. Janatová ¹
Authors‘ workplace: Laboratoř onkogenetiky, Ústav lékařské bio chemie a laboratorní dia gnostiky, 1. LF UK a VFN v Praze ¹; Ústav bio logie a lékařské genetiky, 1. LF UK a VFN v Praze ²; Ústav patologické fyziologie, 1. LF UK, Praha ³; Klinika pediatrie a dědičných metabolických poruch, 1. LF UK a VFN v Praze ⁴
Published in: Klin Onkol 2023; 36(3): 198-205
Category: Review
doi: https://doi.org/10.48095/ccko2023198

Overview

Background: Breast cancer is a complex, multifactorial disease influenced by many genetic factors. Besides the relatively rare pathogenic variants in high or moderate penetrant cancer predisposition genes, breast cancer risk is modified by numerous low risk alleles considered to be polygenic genetic factors. While the risks associated with individual polygenic loci are negligible, its cumulative effect can reach clinically significant values and it can be expressed as a polygenic risk score (PRS). PRS is recently considered to be a possible tool improving assessment of absolute and cumulative risks at the individual level. Purpose: Several single nucleotide polymorphism sets for PRS assessment have recently been developed and prepared for their implementation into clinical practice. The following text aims to explain the fundamental principles of the PRS assessment and its interpretation as a candidate prediction tool. The use of the PRS should always depend on genetic analysis of pathogenic variants in cancer predisposition genes including its current limitations.

Keywords:

breast cancer – risk stratification – polygenic risk score – PRS – breast cancer risk – sporadic breast cancer

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