{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:08:17Z","timestamp":1785391697667,"version":"3.55.0"},"reference-count":18,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      To independently assess data for recently reported genes\u2014\n                      <jats:italic>BIK<\/jats:italic>\n                      ,\n                      <jats:italic>SAMHD1<\/jats:italic>\n                      ,\n                      <jats:italic>FAM111A<\/jats:italic>\n                      , and\n                      <jats:italic>AOX1<\/jats:italic>\n                      \u2014in which rare variants have been associated with prostate cancer (PCa) risk and aggressiveness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study included 4448 PCa cases from Johns Hopkins School of Medicine and 103,221 population\u2010based controls from the Genome Aggregation Database (gnomAD). Gene\u2010based and variant\u2010based association tests were performed within each major ancestry group using Fisher's exact test and Firth logistic regression. Bonferroni\u2010corrected significance thresholds were applied to account for multiple testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Conclusion<\/jats:title>\n                    <jats:p>\n                      In the NFE population, suggestive statistical evidence of association with PCa risk was found for two of the four genes,\n                      <jats:italic>BIK<\/jats:italic>\n                      and\n                      <jats:italic>SAMHD1<\/jats:italic>\n                      . The evidence was primarily driven by missense variants:\n                      <jats:italic>BIK<\/jats:italic>\n                      S87G and\n                      <jats:italic>SAMHD1<\/jats:italic>\n                      Q465K and V112I. The effect sizes of these variants were stronger than, or comparable to, those of well\u2010established PCa risk variants such as\n                      <jats:italic>HOXB13<\/jats:italic>\n                      G84E and\n                      <jats:italic>CHEK2<\/jats:italic>\n                      T367fs. A weak association signal was observed between\n                      <jats:italic>AOX1<\/jats:italic>\n                      and PCa aggressiveness. Statistical power was limited for analyses in other ancestry groups, particularly for tests of PCa aggressiveness. Implication of\n                      <jats:italic>BIK<\/jats:italic>\n                      and\n                      <jats:italic>SAMHD1<\/jats:italic>\n                      as PCa susceptibility genes represents a major breakthrough since the discovery of\n                      <jats:italic>HOXB13<\/jats:italic>\n                      in 2012 and may have clinical utility for risk stratification and contribute to our understanding of the molecular etiology of PCa.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70037","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T18:39:43Z","timestamp":1755542383000},"page":"1556-1561","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Confirmation of\n                    <i>BIK<\/i>\n                    and\n                    <i>SAMHD1<\/i>\n                    as Prostate Cancer Susceptibility Genes"],"prefix":"10.1002","volume":"85","author":[{"given":"Christian P.","family":"Pavlovich","sequence":"first","affiliation":[{"name":"James Buchanan Brady Urological Institute Johns Hopkins School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Program for Genomic Translational Research Endeavor Health Evanston Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Gielzak","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Johns Hopkins School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuqing","family":"Shi","sequence":"additional","affiliation":[{"name":"Program for Genomic Translational Research Endeavor Health Evanston Illinois 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Luo","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Johns Hopkins School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T.","family":"Helfand","sequence":"additional","affiliation":[{"name":"Program for Genomic Translational Research Endeavor Health Evanston Illinois USA"},{"name":"Division of Urology Endeavor Health Evanston Illinois USA"},{"name":"University of Chicago Pritzker School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Isaacs","sequence":"additional","affiliation":[{"name":"James Buchanan Brady Urological Institute Johns Hopkins School of Medicine Baltimore Maryland 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-024-01966-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56944-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.10.022"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603144"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2016.11.033"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2019.12.003"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphg.48"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12863-020-0833-x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24918"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110000"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601425"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23505"},{"key":"e_1_2_7_15_1","first-page":"S2405","article-title":"Discovery 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