{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:52:59Z","timestamp":1787032379754,"version":"build-2736575974"},"reference-count":14,"publisher":"Harborside Press, LLC","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    The\n                    <jats:italic>HOXB13<\/jats:italic>\n                    c.G251G&gt;A:p.G84E (rs138213197) variant is associated with an increased risk of prostate cancer (PrCa); however, its link to aggressive PrCa remains controversial. Limited data from large, population-based cohorts are available to inform genetic counseling and clarify the PrCa risk associated with this variant.\n                    <jats:bold>Patients and Methods:<\/jats:bold>\n                    We identified individuals heterozygous for\n                    <jats:italic>HOXB13<\/jats:italic>\n                    p.G84E or homozygous wild-type among 592,158 male participants in single nucleotide polymorphism genotyping data from the Veterans Health Administration (VA) Million Veteran Program (MVP). Individuals with PrCa were identified, and Cox proportional hazards models were used to estimate age-specific risk of developing PrCa. In a subset of patients who underwent their first prostate biopsy within the VA health system, a multivariable logistic regression model\u2014adjusting for known PrCa risk factors\u2014was used to assess PrCa risk.\n                    <jats:bold>Results:<\/jats:bold>\n                    Of the MVP participants, 1,660 (0.3%) were heterozygous for\n                    <jats:italic>HOXB13<\/jats:italic>\n                    p.G84E. Heterozygosity was significantly associated with risk of any PrCa (hazard ratio [HR], 3.17 [95% CI, 2.90\u20133.46];\n                    <jats:italic>P<\/jats:italic>\n                    &lt;2.0E-16), metastatic PrCa (HR, 2.99 [95% CI, 2.32\u20133.84];\n                    <jats:italic>P<\/jats:italic>\n                    &lt;2.0E-16), and PrCa-specific mortality (HR, 2.63 [95% CI, 1.66\u20134.19];\n                    <jats:italic>P<\/jats:italic>\n                    =4.4E-05). In the subset of MVP participants who underwent prostate biopsy within the VA health system (n=36,321), a multivariable logistic regression model controlling for known PrCa risk factors showed that\n                    <jats:italic>HOXB13<\/jats:italic>\n                    p.G84E heterozygotes had a higher risk of PrCa diagnosis (odds ratio, 2.60 [95% CI, 1.94\u20133.52];\n                    <jats:italic>P<\/jats:italic>\n                    &lt;.001).\n                    <jats:italic>HOXB13<\/jats:italic>\n                    p.G84E heterozygotes were diagnosed with PrCa at a slightly younger age but had similar Gleason score distributions and comparable rates of de novo, any, and castration-resistant metastatic disease.\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    In the largest cohort of men with the\n                    <jats:italic>HOXB13<\/jats:italic>\n                    p.G84E variant studied to date, we demonstrate a moderately increased lifetime risk of PrCa. However, the PrCa that develops is not more aggressive, although it may occur at younger ages. Further research is warranted to determine whether early PrCa screening in\n                    <jats:italic>HOXB13<\/jats:italic>\n                    p.G84E heterozygotes improves outcomes.\n                  <\/jats:p>","DOI":"10.6004\/jnccn.2025.7055","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T18:49:40Z","timestamp":1757962180000},"source":"Crossref","is-referenced-by-count":1,"title":["Association of HOXB13 G84E With Prostate Cancer Among 592,158 Men"],"prefix":"10.6004","volume":"23","author":[{"given":"Taylor B.","family":"Crawford","sequence":"first","affiliation":[{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Nelson","sequence":"additional","affiliation":[{"name":"VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Karunamuni","sequence":"additional","affiliation":[{"name":"Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heena","family":"Desai","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Hausler","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Teerlink","sequence":"additional","affiliation":[{"name":"VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT"},{"name":"Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Carter","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Medicine, University of California, San Diego, La Jolla, CA"},{"name":"Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA"},{"name":"Moores Cancer Center, University of California, San Diego, La Jolla, CA"},{"name":"Cancer Cell Map Initiative (CCMI), University of California, San Diego, La Jolla, CA"},{"name":"CIFAR, MaRS Centre, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghana S.","family":"Pagadala","sequence":"additional","affiliation":[{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA"},{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick R.","family":"Alba","sequence":"additional","affiliation":[{"name":"VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT"},{"name":"Division of Epidemiology, Department of Internal Medical, University of Utah School of Medicine, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"DuVall","sequence":"additional","affiliation":[{"name":"VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT"},{"name":"Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan E.","family":"Danowski","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Brunette","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Ratner","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isla P.","family":"Garraway","sequence":"additional","affiliation":[{"name":"Department of Surgical and Perioperative Care, VA Greater Los Angeles Healthcare System, Los Angeles, CA"},{"name":"Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent S.","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen A.","family":"Cooney","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University School of Medicine, and Duke Cancer Institute, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason L.","family":"Vassy","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System, Boston, MA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA"},{"name":"Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA"},{"name":"Population Precision Health, Ariadne Labs, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Hauger","sequence":"additional","affiliation":[{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA"},{"name":"Center for Behavior Genetics of Aging, School of Medicine, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Lynch","sequence":"additional","affiliation":[{"name":"VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT"},{"name":"Division of Epidemiology, Department of Internal Medical, University of Utah School of Medicine, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler M.","family":"Seibert","sequence":"additional","affiliation":[{"name":"Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, CA"},{"name":"Research Service, VA San Diego Healthcare System, San Diego, CA"},{"name":"Department of Bioengineering, University of California, San Diego, La Jolla, CA"},{"name":"Department of Radiology, University of California, San Diego, La Jolla, CA"},{"name":"Department of Urology, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara N.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA"},{"name":"Division of Hematology\/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","series-title":"N Engl J Med","first-page":"1547","article-title":"10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer","volume":"388","author":"Hamdy FC","year":"2023","unstructured":"Hamdy FC, Donovan JL, Lane JA,  10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. 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JCO Clin Cancer Inform 2021;5:1005\u20131014."},{"key":"B12","series-title":"J Natl Cancer Inst","first-page":"753","article-title":"Genetic risk and likelihood of prostate cancer detection on first biopsy by ancestry","volume":"116","author":"Lee KM","year":"2024","unstructured":"Lee KM, Nelson TJ, Bryant A,  Genetic risk and likelihood of prostate cancer detection on first biopsy by ancestry. J Natl Cancer Inst 2024;116:753\u2013757."},{"key":"B13","series-title":"J Natl Cancer Inst","first-page":"190","article-title":"Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program","volume":"115","author":"Pagadala MS","year":"2023","unstructured":"Pagadala MS, Lynch J, Karunamuni R,  Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program. J Natl Cancer Inst 2023;115:190\u2013199."},{"key":"B14","series-title":"J Natl Compr Canc Netw","first-page":"237","article-title":"Racial differences in germline genetic testing completion among males with pancreatic, breast, or metastatic prostate cancers","volume":"22","author":"Shevach JW","year":"2024","unstructured":"Shevach JW, Candelieri-Surette D, Lynch JA,  Racial differences in germline genetic testing completion among males with pancreatic, breast, or metastatic prostate cancers. J Natl Compr Canc Netw 2024;22:237\u2013243."}],"container-title":["Journal of the National Comprehensive Cancer Network"],"original-title":[],"link":[{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/23\/10\/article-e257055.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/23\/10\/article-e257055.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/23\/10\/article-e257055.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:35:39Z","timestamp":1760013339000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/23\/10\/article-e257055.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":14,"journal-issue":{"issue":"10"},"URL":"https:\/\/doi.org\/10.6004\/jnccn.2025.7055","relation":{},"ISSN":["1540-1405","1540-1413"],"issn-type":[{"value":"1540-1405","type":"print"},{"value":"1540-1413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]}}}