Prostate cancer screening is crucial for attenuating morbidity and
mortality22 23 2425. However, the traditional method of PSA screening
is infamous for false-positive rate and potential harm due to
overtreatment of benign disease2627. The US Preventive Service Task Force recommended
the consideration of family history and race/ethnicity to identify men
who would benefit the most from early PSA screening. While family
history and race/ethnicity are indirect assessments of inherited risk,
which can be prone to environmental exposures, PRS creates an
opportunity to directly measure inherited PCa risk. A cohort study of
3225 men showed that PRS acts as an independent predictor for PCa;
thereby, incorporating PRS into the current risk prediction model based
on family history, PSA and age could create a better stratification tool
with improved predictive capacity2728. Even among
unbiopsied men with low level of serum PSA of 1-3 ng/ml, PRS can be used
to predict biopsy outcomes and identify men with high PCa
risk29. PRS’s predictive power offers an informative
tool to target PSA screening efforts for men with a higher risk of early
PCa onset and to guide decisions for a more active clinical approach to
those with a higher risk of aggressive PCa2730 (Figure 1) Additionally, there is evidence
indicating that the cumulative effect of known polygenic risk factors
can modify the risk estimate of mutations in BRCA1 and BRCA2, with
penetrance of BRCA1 and BRCA2 varying as much as 26% and 61%
respectively, depending on whether the individual is at the 5th or 95th
percentile of prostate cancer31.
Figure 1: Utilization of PRS to predict individual risk
of prostate cancer (Created using BioRender.com)