{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:28:28Z","timestamp":1780504108099,"version":"3.54.1"},"reference-count":67,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>Considerable genetic heterogeneity is currently thought to underlie hereditary prostate cancer (HPC). Most families meeting criteria for HPC cannot be attributed to currently known pathogenic variants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>To discover pathogenic variants predisposing to prostate cancer, we conducted a familial case-control association study using both genome-wide single-allele and identity-by-descent analytic approaches. Sequence of high-risk haplotype carriers was used for variant detection. Candidate pathogenic variants were tested for association with prostate cancer across independent biobanks for replication of observations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Pathogenic variants within\n              <jats:italic>WNT9B<\/jats:italic>\n              were associated with familial prostate cancer and observations replicated within four of four independent biobanks.\n              <jats:italic>WNT9B<\/jats:italic>\n              E152K carried 2.5-fold risk and reached genome-wide significance under meta-analysis, collectively encompassing a half million patients.\n              <jats:italic>WNT9B<\/jats:italic>\n              Q47R was also associated with prostate cancer with genome-wide significance among Finns, for which identity-by-descent analyses confirmed a founder effect.\n              <jats:italic>WNT9B<\/jats:italic>\n              shares an unexpected commonality with the previously established prostate cancer risk genes\n              <jats:italic>HOXB13<\/jats:italic>\n              and\n              <jats:italic>HNF1B<\/jats:italic>\n              : they are each required for embryonic prostate development. With this recognition, we further evaluated two additional genes known to cause Mendelian genitourinary developmental defects,\n              <jats:italic>KMT2D<\/jats:italic>\n              and\n              <jats:italic>DHCR7<\/jats:italic>\n              . These too were nominally associated with prostate cancer under meta-analyses.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              <jats:italic>WNT9B<\/jats:italic>\n              and additional genes that are required for early genitourinary development are also involved in the later development of prostate cancer.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-24-00569","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T20:59:15Z","timestamp":1738097955000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Coding Variants of the Genitourinary Development Gene\n            <i>WNT9B<\/i>\n            Carry High Risk for Prostate Cancer"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8166-599X","authenticated-orcid":true,"given":"William D.","family":"Dupont","sequence":"first","affiliation":[{"name":"Medical Research Service, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN"},{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-4360","authenticated-orcid":true,"given":"Angela L.","family":"Jones","sequence":"additional","affiliation":[{"name":"Vanderbilt Technologies for Advanced Genomics, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"VA Million Veteran Program","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-910X","authenticated-orcid":true,"given":"Jeffrey R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Medical Research Service, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN"},{"name":"Department of Medicine, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.8.3367"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)35617-3"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027130"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0895-827"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/301862"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11128"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/320114"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20433"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-12-0495"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.01.019"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-89399-7"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15122-1"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110000"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2437"},{"key":"e_1_3_7_16_2","first-page":"4513","article-title":"The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. 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