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Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry
- Source :
- European Urology, European Urology, 2023, 84 (1), pp.13-21. ⟨10.1016/j.eururo.2023.01.022⟩
- Publication Year :
- 2023
- Publisher :
- Elsevier BV, 2023.
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Abstract
- Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.Design, setting, and participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.Outcome measurements and statistical analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.Results and limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4).Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.Patient summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.
- Subjects :
- Prostate cancer
MESH: Humans
Urology
MESH: Genetic Predisposition to Disease
MESH: Black People
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
MESH: Male
Polygenic risk score
African ancestry
MESH: Risk Factors
MESH: Prostatic Neoplasms
MESH: Genome-Wide Association Study
Susceptibility loci
Aggressive prostate cancer
Subjects
Details
- ISSN :
- 03022838 and 1421993X
- Database :
- OpenAIRE
- Journal :
- European Urology
- Accession number :
- edsair.doi.dedup.....7b42ff56b071fb413155ed348022ab4c