ArticleBMC cancer2022
PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- VADEr: Vision Transformer-Inspired Framework for Polygenic Risk Reveals Underlying Genetic Heterogeneity in Prostate Cancer.medRxiv : the preprint server for health sciences · 2025Article
- Exploring prostate-specific antigen (PSA) Testing rates and screening disparities in the all of us dataset.Urologic oncology · 2025Article
- Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa.Nature genetics · 2024Article
- PCAT19: the role in cancer pathogenesis and beyond.Frontiers in cell and developmental biology · 2024Review
- Heterogeneous genetic architectures and evolutionary genomics of prostate cancer in Sub-Saharan Africa.Research square · 2023Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundProstate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance.
methodsAfrican ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis.
resultsWe identified 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, achieving an AUC of 0.61 [0.60-0.63] and 0.65 [0.64-0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. 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.
conclusionsAfrican ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. 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.
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