Polygenic risk score for genetic evaluation of prostate cancer risk in Asian populations: A narrative review

Abstract

Decreasing costs of genetic testing and interest in disease inheritance has changed the landscape of cancer prediction in prostate cancer (PCa), and guidelines now include genetic testing for high-risk groups. Familial and hereditary PCa comprises approximately 20% and 5% of all PCa, respectively. Multifaceted disorders like PCa are caused by a combinatory effect of rare genes of high penetrance and smaller genetic variants of relatively lower effect size. Polygenic risk score (PRS) is a novel tool utilizing PCa-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association study (GWAS) to generate an additive estimate of an individual's lifetime genetic risk for cancer. However, most PRS are developed based on GWAS collected from mainly European populations and do not address ethnic differences in PCa genetics. This review highlights the attempts to generate a PRS tailored to Asian males including data from Korea, China, and Japan, and discuss the clinical implications for prediction of early onset and aggressive PCa.

Keywords: Multifactorial inheritance; Polygenic traits; Prostatic neoplasms.

Fig. 1. Genetic risk to clinical practice. The calculated lifetime risk of PCa based on PRS allows for selection of high-risk patients for early intervention such as lower PSA thresholds for prostate biopsy. Patients stratified to low-risk may be able to avoid unnecessary screening procedures and be eligible for more non-invasive treatment options such as active surveillance. GWAS, genome-wide association study; PRS, polygenic risk scores; PCa, prostate cancer; PSA, prostate specific antigen.