Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations

作者：Fei Chen, Burcu F. Darst, Ravi Madduri, Alex A Rodriguez, Xin Sheng, Christopher T. Rentsch, Caroline Andrews, Wei Tang, Adam S. Kibel, Anna Plym, Kelly Cho, Mohamed Jalloh, Sérigne Maguèye Gueye, Lamine Niang, Olufemi J. Ogunbiyi, Olufemi Popoola, Akindele O. Adebiyi, Oseremen I. Aisuodionoe-Shadrach, Hafees O. Ajibola, Mustapha A. Jamda, Olabode P. Oluwole, Maxwell M. Nwegbu, Ben Adusei, Sunny Mante, Afua O.D. Abrahams, James E. Mensah, Andrew A. Adjei, Halimatou Diop‐Ndiaye, Joseph Lachance, Timothy R. Rebbeck, Stefan Ambs, J. Michael Gaziano, Amy C. Justice, David V. Conti, Christopher A. Haiman · 发表于：eLife · 年份：2022 · DOI：10.7554/elife.78304 · 被引用次数：35 · 研究领域：Prostate Cancer Diagnosis and Treatment、Genetic Associations and Epidemiology、Prostate Cancer Treatment and Research

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than ...