Validation of a prostate cancer polygenic risk score

Area of Science:

• Genetics
• Oncology
• Epidemiology

Background:

• Genome-wide association studies have identified over 100 single-nucleotide polymorphisms (SNPs) linked to prostate cancer (PrCa).
• Polygenic risk scores (PRS) aggregate genotypes from these SNPs for cancer risk stratification.
• The study evaluated the utility of PRS in a large, multi-site prostate cancer cohort.

Purpose of the Study:

• To assess the contribution of a 72-SNP polygenic risk score (PRS) to prostate cancer (PrCa) risk.
• To validate the predictive performance of PRS in a large, multisite study population.
• To determine the potential of PRS for clinical risk assessment in prostate cancer.

Main Methods:

• A cohort of 1972 PrCa cases and 1919 controls was analyzed.
• Next-generation sequencing identified pathogenic variants in susceptibility genes and 72 validated PrCa-associated SNPs.
• A population-standardized PRS was constructed and its association with PrCa risk was tested using logistic regression, adjusted for age and family history.

Main Results:

• The PRS was significantly higher in PrCa cases compared to controls (P < .0001).
• Men in the highest quartile of PRS had nearly four times the odds of developing PrCa compared to the lowest quartile (OR = 3.98, P < .0001).
• The PRS demonstrated predictive performance consistent with prior literature (AUC = 0.64).

Conclusions:

• A 72-SNP PRS is a significant predictor of prostate cancer risk.
• The findings support the potential clinical utility of PRS for prostate cancer risk assessment.
• PRS may enhance the stratification of individuals at high risk for prostate cancer.