{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:46:14Z","timestamp":1790880374996,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Genome\u2010wide association studies have identified over 100 single\u2010nucleotide polymorphisms (SNPs) associated with prostate cancer (PrCa), and polygenic risk scores (PRS) based on their combined genotypes have been developed for risk stratification. We aimed to assess the contribution of PRS to PrCa risk in a large multisite study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The sample included 1972 PrCa cases and 1919 unaffected controls. Next\u2010generation sequencing was used to assess pathogenic variants in 14 PrCa\u2010susceptibility genes and 72 validated PrCa\u2010associated SNPs. We constructed a population\u2010standardized PRS and tested its association with PrCa using logistic regression adjusted for age and family history of PrCa.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean age of PrCa cases at diagnosis and age of controls at testing\/last clinic visit was 59.5\u2009\u00b1\u20097.2 and 57.2\u2009\u00b1\u200913.0 years, respectively. Among 1740 cases with pathology data, 57.4% had Gleason score\u2009\u2264\u20096, while 42.6% had Gleason score\u2009\u2265\u20098. In addition, 39.6% cases and 20.1% controls had a family history of PrCa. The PRS was significantly higher in cases than controls (mean\u2009\u00b1\u2009SD: 1.42\u2009\u00b1\u20091.11 vs 1.02\u2009\u00b1\u20090.76; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001). Compared with men in the 1st quartile of age\u2010adjusted PRS, those in the 2nd, 3rd, and 4th quartile were 1.58 (95% confidence interval [CI]: 1.31\u20101.90), 2.36 (95% CI: 1.96\u20102.84), and 3.98 (95% CI: 3.29\u20104.82) times as likely to have PrCa (all <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001). Adjustment for family history yielded similar results. PRS predictive performance was consistent with prior literature (area under the receiver operating curve\u2009=\u20090.64; 95% CI: 0.62\u20100.66).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that a 72\u2010SNP PRS is predictive of PrCa, supporting its potential use in clinical risk assessment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24058","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T13:53:26Z","timestamp":1598622806000},"page":"1314-1321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Validation of a prostate cancer polygenic risk score"],"prefix":"10.1002","volume":"80","author":[{"given":"Mary H.","family":"Black","sequence":"first","affiliation":[{"name":"Ambry Genetics Aliso Viejo 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James Buchanan Brady Urologic Institute Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6321-950X","authenticated-orcid":false,"given":"Zhuqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University Health System Evanston Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University Health System Evanston Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqun Lilly","family":"Zheng","sequence":"additional","affiliation":[{"name":"Program for Personalized Cancer Care NorthShore University Health System Evanston Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian 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