Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations.
Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations.
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DOI：
10.7554/elife.78304
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发表时间：
2022-07-08
期刊：
影响因子：
7.7
通讯作者：
Haiman, Christopher A.
中科院分区：
文献类型：
--
作者：
Chen, Fei;Darst, Burcu F.;Madduri, Ravi K.;Rodriguez, Alex A.;Sheng, Xin;Rentsch, Christopher T.;Andrews, Caroline;Tang, Wei;Kibel, Adam S.;Plym, Anna;Cho, Kelly;Jalloh, Mohamed;Gueye, Serigne Magueye;Niang, Lamine;Ogunbiyi, Olufemi J.;Popoola, Olufemi;Adebiyi, Akindele O.;Aisuodionoe-Shadrach, Oseremen, I;Ajibola, Hafees O.;Jamda, Mustapha A.;Oluwole, Olabode P.;Nwegbu, Maxwell;Adusei, Ben;Mante, Sunny;Darkwa-Abrahams, Afua;Mensah, James E.;Adjei, Andrew Anthony;Diop, Halimatou;Lachance, Joseph;Rebbeck, Timothy R.;Ambs, Stefan;Gaziano, J. Michael;Justice, Amy C.;Conti, David, V;Haiman, Christopher A.
我们最近开发了一种多血统多基因风险评分（PRS），它能有效地对不同人群的前列腺癌风险进行分层。在这项研究中，我们在多血统的“百万退伍军人计划”以及其他独立研究中验证了PRS的性能。
在每个血统人群中，在每个病例 - 对照研究中分别评估了PRS与前列腺癌风险的关联，然后在固定效应逆方差加权荟萃分析中进行合并。我们进一步评估了年龄对效应的修饰作用，并估计了每个血统人群前列腺癌的年龄特异性绝对风险。
PRS在31,925例病例和490,507例对照中进行了评估，包括来自欧洲（22,049例病例，414,249例对照）、非洲（8794例病例，55,657例对照）和西班牙裔（1082例病例，20,601例对照）人群的男性。将PRS处于最高十分位数（90 - 100%）的男性与PRS处于平均40 - 60%类别的男性相比，欧洲血统男性的前列腺癌优势比（OR）为3.8倍（95%置信区间 = 3.62 - 3.96），非洲血统男性为2.8倍（95%置信区间 = 2.59 - 3.03），西班牙裔男性为3.2倍（95%置信区间 = 2.64 - 3.92）。PRS不能区分侵袭性与非侵袭性前列腺癌的风险。然而，OR随着年龄的增长而降低（欧洲血统男性中处于最高十分位数者：≤55岁，OR = 7.11；55 - 60岁，OR = 4.26；>70岁，OR = 2.79）。PRS处于最高十分位数的男性达到5%的前列腺癌绝对风险比PRS处于40 - 60%类别的男性大约年轻10岁。
我们的研究结果验证了多血统PRS作为一种跨人群有效的前列腺癌风险分层工具。有必要对PRS进行一项临床研究，以确定PRS是否可用于风险分层筛查和早期检测。
这项工作得到了美国国立卫生研究院国家癌症研究所（授予C.A.H.的资助编号为U19 CA214253、U01 CA257328、U19 CA148537、R01 CA165862，授予B.F.D的K99 CA246063，授予F.C的T32CA229110）、前列腺癌基金会（授予B.F.D的21YOUN11和授予C.A.H.的20CHAS03）、洛杉矶创始人分会美国大学科学家成就奖励基金会对B.F.D的资助，以及百万退伍军人计划 - MVP017的支持。这项研究是使用英国生物银行资源（申请编号42195）进行的。这项研究基于百万退伍军人计划、研究与发展办公室以及退伍军人健康管理局的数据。本出版物不代表退伍军人事务部或美国政府的观点。
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. 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. 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 men in the 40–60% PRS category. Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.