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Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate cancer families (4.6 %), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of K. A. Cooney and W. B. Isaacs are Co-Senior Authors.","publication_date":"2013,,","publication_name":"Human Genetics","grobid_abstract_attachment_id":"46037455"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG)","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [31600762]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 'edu.academia.applesignon';</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div 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PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG)</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="31600762" href="https://independent.academia.edu/NancyHamel"><img alt="Profile image of Nancy Hamel" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Nancy Hamel</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2013, Human Genetics</p></div><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" 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data-landing_url="https://www.academia.edu/12632501/HOXB13_is_a_susceptibility_gene_for_prostate_cancer_results_from_the_International_Consortium_for_Prostate_Cancer_Genetics_ICPCG_" data-login_uri="https://www.academia.edu/registrations/google_one_tap" data-moment_callback="onGoogleOneTapEvent" id="g_id_onload"></div><div class="ds-top-related-works--grid-container"><div class="ds-related-content--container ds-top-related-works--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="19438695" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/19438695/HOXB13_Mutation_and_Prostate_Cancer_Studies_of_Siblings_and_Aggressive_Disease">HOXB13 Mutation and Prostate Cancer: Studies of Siblings and Aggressive Disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39707546" href="https://independent.academia.edu/Mefford">Joel Mefford</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Epidemiology Biomarkers & Prevention, 2013</p><p class="ds-related-work--abstract ds2-5-body-sm">Recent work detected for the first time a high-risk prostate cancer mutation, in homeobox B13 (HOXB13) among European-Americans. We further evaluated this G84E missense mutation (rs138213197) in two genetic association studies of prostate cancer: a family-based study of brothers and a case-control study of more aggressive disease (N = 2,665 total). We then calculated overall impact of this mutation by pooling all published studies of European-Americans. In our studies, the mutation was found exclusively among men with prostate cancer (carrier frequency = 1.48%) or unaffected brothers of cases carrying the mutation (frequency = 0.34%), and carrying the mutation gave an OR for disease = 4.79 (P = 0.01). The G84E mutation was more common among men with an earlier age of onset (≤55 years) or a family history of prostate cancer. We also observed for the first time an African-American case carrying the G84E mutation, although at HOXB13 both of his chromosomes were of European-American ancestry. The pooled analysis also indicated that carrying the G84E mutation results in an almost five-fold increase in risk of prostate cancer (P = 3.5 × 10(-17)), and this risk is even higher among cases with an early age of prostate cancer onset (≤55 years) or a family history of disease: a test of heterogeneity across these strata gives P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 1 × 10(-5). The HOXB13 mutation substantially increases risk of early onset, familial prostate cancer in European-American men. 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class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/89029209/HOXB13_G84E_related_Familial_Prostate_Cancers"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="106422357" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/106422357/Identification_of_Two_Novel_HOXB13_Germline_Mutations_in_Portuguese_Prostate_Cancer_Patients">Identification of Two Novel HOXB13 Germline Mutations in Portuguese Prostate Cancer Patients</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="4667926" href="https://independent.academia.edu/JorgeOliveira3">Jorge Oliveira</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PloS one, 2015</p><p class="ds-related-work--abstract ds2-5-body-sm">The HOXB13 germline variant G84E (rs138213197) was recently described in men of European descent, with the highest prevalence in Northern Europe. The G84E mutation has not been found in patients of African or Asian ancestry, which may carry other HOXB13 variants, indicating allelic heterogeneity depending on the population. In order to gain insight into the full scope of coding HOXB13 mutations in Portuguese prostate cancer patients, we decided to sequence the entire coding region of the HOXB13 gene in 462 early-onset or familial/hereditary cases. Additionally, we searched for somatic HOXB13 mutations in 178 prostate carcinomas to evaluate their prevalence in prostate carcinogenesis. Three different patients were found to carry in their germline DNA two novel missense variants, which were not identified in 132 control subjects. Both variants are predicted to be deleterious by different in silico tools. No somatic mutations were found. These findings further support the hypothesis th...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Identification of Two Novel HOXB13 Germline Mutations in Portuguese Prostate Cancer Patients","attachmentId":105624936,"attachmentType":"pdf","work_url":"https://www.academia.edu/106422357/Identification_of_Two_Novel_HOXB13_Germline_Mutations_in_Portuguese_Prostate_Cancer_Patients","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/106422357/Identification_of_Two_Novel_HOXB13_Germline_Mutations_in_Portuguese_Prostate_Cancer_Patients"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="20243615" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/20243615/Fine_Mapping_the_HOXB_Region_Detects_Common_Variants_Tagging_a_Rare_Coding_Allele_Evidence_for_Synthetic_Association_in_Prostate_Cancer">Fine-Mapping the HOXB Region Detects Common Variants Tagging a Rare Coding Allele: Evidence for Synthetic Association in Prostate Cancer</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32585343" href="https://independent.academia.edu/RadkaKaneva">Radka Kaneva</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PLoS Genetics, 2014</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Fine-Mapping the HOXB Region Detects Common Variants Tagging a Rare Coding Allele: Evidence for Synthetic Association in Prostate Cancer","attachmentId":41226936,"attachmentType":"pdf","work_url":"https://www.academia.edu/20243615/Fine_Mapping_the_HOXB_Region_Detects_Common_Variants_Tagging_a_Rare_Coding_Allele_Evidence_for_Synthetic_Association_in_Prostate_Cancer","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/20243615/Fine_Mapping_the_HOXB_Region_Detects_Common_Variants_Tagging_a_Rare_Coding_Allele_Evidence_for_Synthetic_Association_in_Prostate_Cancer"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="76236509" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/76236509/Oncogenic_mechanisms_of_HOXB13_missense_mutations_in_prostate_carcinogenesis">Oncogenic mechanisms of HOXB13 missense mutations in prostate carcinogenesis</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="134377786" href="https://independent.academia.edu/PaulaPaulo4">Paula Paulo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Oncoscience, 2016</p><p class="ds-related-work--abstract ds2-5-body-sm">The recurrent germline mutation HOXB13 p.(Gly84Glu) (G84E) has recently been identified as a risk factor for prostate cancer. In a recent study, we have performed full sequencing of the HOXB13 gene in 462 Portuguese prostate cancer patients with early-onset and/or familial/hereditary disease, and identified two novel missense mutations, p.(Ala128Asp) (A128D) and p.(Phe240Leu) (F240L), that were predicted to be damaging to protein function. In the present work we aimed to investigate the potential oncogenic role of these mutations, comparing to that of the recurrent G84E mutation and wild-type HOXB13. We induced site-directed mutagenesis in a HOXB13 expression vector and established in vitro cell models of prostate carcinogenesis with stable overexpression of either the wild-type or the mutated HOXB13 variants. By performing in vitro assays we observed that, while the wild-type promotes proliferation, also observed with the F240L variant along with a decrease in apoptosis, the A128D ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Oncogenic mechanisms of HOXB13 missense mutations in prostate carcinogenesis","attachmentId":83975064,"attachmentType":"pdf","work_url":"https://www.academia.edu/76236509/Oncogenic_mechanisms_of_HOXB13_missense_mutations_in_prostate_carcinogenesis","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/76236509/Oncogenic_mechanisms_of_HOXB13_missense_mutations_in_prostate_carcinogenesis"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="54703034" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/54703034/Association_of_homeobox_B13_HOXB13_gene_variants_with_prostate_cancer_risk_in_an_Iranian_population">Association of homeobox B13 (HOXB13) gene variants with prostate cancer risk in an Iranian population</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="193462622" href="https://independent.academia.edu/RahelehRoudi">Raheleh Roudi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Medical Journal of the Islamic Republic of Iran</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Association of homeobox B13 (HOXB13) gene variants with prostate cancer risk in an Iranian population","attachmentId":70941006,"attachmentType":"pdf","work_url":"https://www.academia.edu/54703034/Association_of_homeobox_B13_HOXB13_gene_variants_with_prostate_cancer_risk_in_an_Iranian_population","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/54703034/Association_of_homeobox_B13_HOXB13_gene_variants_with_prostate_cancer_risk_in_an_Iranian_population"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":46037455,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":46037455,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_46037455" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="52504478" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/52504478/Association_of_Homeobox_B13_HOXB13_Gene_Variants_with_Prostate_Cancer_Risk_in_Iranian_Population">Association of Homeobox B13 (HOXB13) Gene Variants with Prostate Cancer Risk in Iranian Population</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="193462622" href="https://independent.academia.edu/RahelehRoudi">Raheleh Roudi</a></div><div class="ds-related-work--ctas"><button 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ds2-5-body-link" href="https://www.academia.edu/22224171/Imputation_of_the_Rare_HOXB13_G84E_Mutation_and_Cancer_Risk_in_a_Large_Population_Based_Cohort">Imputation of the Rare HOXB13 G84E Mutation and Cancer Risk in a Large Population-Based Cohort</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="43586841" href="https://independent.academia.edu/MarkKvale">Mark Kvale</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PLOS Genetics, 2015</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Imputation of the Rare HOXB13 G84E Mutation and Cancer Risk in a Large Population-Based 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translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/72346302/Genetic_epidemiology_of_prostate_cancer"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="6" data-entity-id="83372513" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/83372513/Presence_of_G84E_Allelic_Heterogeneity_of_the_European_Prostate_Cancer_SNP_Mutation_of_HOX13B_G84E_Associated_with_the_European_R_Haplogroup_of_Y_Chromosome_and_Absence_of_Gene_Flow_into_Moroccans_Patients">Presence of G84E Allelic Heterogeneity of the European Prostate Cancer SNP Mutation of HOX13B-G84E Associated with the European R-Haplogroup of Y-Chromosome and Absence of Gene Flow into Moroccans Patients</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="36358065" href="https://univh2.academia.edu/MoulayMustaphaEnnaji">Moulay Mustapha Ennaji</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biosciences and Medicines, 2021</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Presence of G84E Allelic Heterogeneity of the European Prostate Cancer SNP Mutation of HOX13B-G84E Associated with the European R-Haplogroup of Y-Chromosome and Absence of Gene Flow into Moroccans 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