{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T01:28:01Z","timestamp":1762997281253},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,9,21]],"date-time":"2010-09-21T00:00:00Z","timestamp":1285027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Several reports suggest that a combination of risk alleles may be associated with prostate cancer (CaP) risk and tumor features. However, their ability to detect CaP and tumor characteristics in patients with a \u201cnormal\u201d PSA (&lt;4\u2009ng\/ml) and non\u2010suspicious digital rectal examination (DRE) remains to be determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We examined 203 men of European ancestry with clinical stage T1c CaP diagnosed at a \u201cnormal\u201d PSA and 611 healthy volunteer controls. The genotypes for 17 different risk alleles were compared between CaP cases and controls. Additional analyses were used to compare the pathologic features between carriers and non\u2010carriers (defined using best\u2010fit genetic model) of these variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>All risk alleles were present at an increased frequency in cases with \u201cnormal\u201d PSA values and DRE compared to controls. Amongst CaP patients, carriers of an increasing number of genetic risk factors (i.e., alleles and positive family history) were at a significantly increased risk of CaP (<jats:italic>P<\/jats:italic>\u2010trend &lt;0.001). Specifically, men with &gt;10 genetic risk factors had an 11.2\u2010fold risk (95% CI 4.3\u201329.2) of having the disease compared to men with \u22645 variants. There also was a higher frequency of many the variants amongst men with adverse pathologic features.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>A substantial proportion of biopsy\u2010detectable CaP occurs in men with \u201cnormal\u201d PSA levels and negative DRE. In this population, CaP risk alleles and family history are significantly associated with CaP risk and may help predict aggressive disease. Future studies are warranted to determine the utility of incorporating these variants into CaP screening programs. Prostate 77:394\u2013402, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.21253","type":"journal-article","created":{"date-parts":[[2010,9,21]],"date-time":"2010-09-21T13:19:13Z","timestamp":1285075153000},"page":"394-402","source":"Crossref","is-referenced-by-count":15,"title":["Prostate cancer risk alleles significantly improve disease detection and are associated with aggressive features in patients with a \u201cnormal\u201d prostate specific antigen and digital rectal examination"],"prefix":"10.1002","volume":"71","author":[{"given":"Brian T.","family":"Helfand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghui","family":"Kan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parth","family":"Modi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Catalona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,9,21]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2351"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030660"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031918"},{"issue":"3","key":"e_1_2_7_5_2","first-page":"113","article-title":"Twenty years of PSA: From prostate antigen to tumor marker","volume":"9","author":"De Angelis G","year":"2007","journal-title":"Rev 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