A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Study Design
2.2. Genotyping
2.3. Endpoint
2.4. Calculation of Polygenic Risk Score
2.5. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Prostate Cancer Diagnoses
3.3. Association of PRS with Incident Prostate Cancer Risk
3.4. Prevalent Prostate Cancer
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | ASPREE |
---|---|
Participants | 5701 |
Age at randomisation (mean (SD)) | 74.9 (4.2) |
Age Group (%) | |
70–74 | 3566 (62.6) |
75–79 | 1384 (24.3) |
80–84 | 585 (10.3) |
85+ | 166 (2.9) |
Current or former smoker (%) | 3203 (56.2) |
Diabetes (%) | 637 (11.2) |
Randomized to Aspirin (%) | 2837 (49.8) |
Body-mass-index (kg/m2) − mean (SD) | 27.9 (3.8) |
Current alcohol consumption (%) | 4880 (85.6) |
Family history of prostate cancer (%) | 499 (8.8) |
Polygenic Risk Score − mean (SD) | −0.46 (0.15) |
Prevalent Prostate Cancer (%) (self-reported at enrolment) | |
None | 4725 (88.5) |
<49 years | 4 (0.0) |
≥50 years | 654 (11.5) |
Incident prostate cancer. (218 clinically confirmed cases during the ASPREE trial, excluding all prevalent cases) | ||||||
Variable | PRS as Continuous Variable (per Standard Deviation) | PRS as Categorical Variable (low, medium, high) | ||||
Hazard Ratio | 95% CI | p-Value | Hazard Ratio | 95% CI | p-Value | |
PRS (per std dev) | 1.52 | (1.33; 1.74) | <0.0001 | |||
Low PRS 0–20% (n = 23) | Reference | |||||
Medium PRS >20–80% (n = 128) | 1.74 | (1.14; 2.66) | 0.01 | |||
High PRS >80% (n = 57) | 2.99 | (1.90; 4.72) | <0.0001 |
Incident prostate cancer in participants with age at randomisation between 70 and 74 years (126 clinically confirmed cases during the ASPREE trial, excluding all prevalent cases) | ||||||
Variable | PRS as Continuous Variable (per Standard Deviation) | PRS as Categorical Variable (low, medium, high) | ||||
Hazard Ratio | 95% CI | p-Value | Hazard Ratio | 95% CI | p-Value | |
PRS (per std dev) | 1.65 | (1.39; 1.97) | <0.0001 | |||
Low PRS 0–20% (n = 23) | Reference | |||||
Medium PRS >20–80% (n = 128) | 1.78 | (1.00; 3.15) | 0.05 | |||
High PRS >80% (n = 57) | 3.54 | (1.93; 6.49) | <0.0001 |
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Bakshi, A.; Riaz, M.; Orchard, S.G.; Carr, P.R.; Joshi, A.D.; Cao, Y.; Rebello, R.; Nguyen-Dumont, T.; Southey, M.C.; Millar, J.L.; et al. A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease. Cancers 2021, 13, 5815. https://doi.org/10.3390/cancers13225815
Bakshi A, Riaz M, Orchard SG, Carr PR, Joshi AD, Cao Y, Rebello R, Nguyen-Dumont T, Southey MC, Millar JL, et al. A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease. Cancers. 2021; 13(22):5815. https://doi.org/10.3390/cancers13225815
Chicago/Turabian StyleBakshi, Andrew, Moeen Riaz, Suzanne G. Orchard, Prudence R. Carr, Amit D. Joshi, Yin Cao, Richard Rebello, Tú Nguyen-Dumont, Melissa C. Southey, Jeremy L. Millar, and et al. 2021. "A Polygenic Risk Score Predicts Incident Prostate Cancer Risk in Older Men but Does Not Select for Clinically Significant Disease" Cancers 13, no. 22: 5815. https://doi.org/10.3390/cancers13225815