Understanding the Biological Basis of Polygenic Risk Scores and Disparities in Prostate Cancer: A Comprehensive Genomic Analysis
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View abstract on PubMed
Summary
This summary is machine-generated.Polygenic risk scores (PRS) for prostate cancer (PCa) link genetic variants to molecular mechanisms and racial disparities. PRS is a useful metric but has limitations in explaining PCa and its disparities.
Area Of Science
- Genomics and Molecular Biology
- Cancer Research
- Population Genetics
Background
- Hundreds of prostate cancer (PCa) risk variants are known, but their collective relevance to molecular carcinogenesis and racial disparities remains unclear.
- The utility of a polygenic risk score (PRS) in reflecting underlying biological mechanisms and population differences in PCa is not well understood.
Purpose Of The Study
- To investigate the biological basis of PRS in prostate cancer.
- To understand the role of PRS in racial disparities observed in prostate cancer.
- To assess the association between PRS and molecular mechanisms of prostate carcinogenesis.
Main Methods
- Constructed PRS using 260 PCa risk variants from a trans-ancestry meta-analysis.
- Analyzed genomic and transcriptomic data from GTEx, TCGA, 1000 Genomes, GEO, and dbGap.
- Examined PRS association with gene expression in normal prostate tissues and its correlation with signaling pathways.
Main Results
- Identified 540 PRS-associated genes in normal prostate samples from European Americans (EAs).
- Observed increased ubiquitin-proteasome system activity in high-PRS individuals.
- Found nine PRS genes involved in key cancer signaling pathways (PI3K-Akt/RAS-MAPK/mTOR) and frequently mutated in PCa.
- Demonstrated PRS gene expression profiles predict PCa relapse post-prostatectomy.
- Noted transcriptomic differences between African American and EA samples were inconsistent with PRS-gene expression associations.
Conclusions
- PRS offers insights into prostate cancer's molecular mechanisms and heritability.
- PRS has both utility and limitations in explaining PCa susceptibility and observed racial disparities.
- Further research is needed to fully elucidate the role of PRS in prostate cancer etiology and population differences.
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