Genetic Risk Scoring in Prostate Cancer for Men of African Ancestry

An African ancestry-specific prostate cancer (PrCa) polygenic risk score (PRState) can successfully predict the risk of PrCa in men of African ancestry, according to a study published in BMC Cancer.

“Men of African ancestry are at an increased risk of PrCa; however, current (PRS) models are based on European ancestry groups and may not be broadly applicable,” the investigators said.

In this study, data on 4,533 men of African ancestry were used for discovery of African ancestry specific PrCa single nucleotide polymorphisms (SNPs). The investigators assessed performance using ROC-AUC analysis.

According to the results, African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieved an AUC of 0.61 [0.60-0.63] and 0.65 [0.64-0.67], when combined with age and family history, the researchers noted. They observed that the risk scoring performance notably declined when using ancestry mismatched PRS models, but remained comparable when using trans-ancestry models. The investigators said that: “Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry.”

“African ancestry-specific PRState improves PrCa prediction in African ancestry groups,” the researchers concluded. “This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies.”