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dc.contributor.authorDarst, BF
dc.contributor.authorHughley, R
dc.contributor.authorPfennig, A
dc.contributor.authorHazra, U
dc.contributor.authorFan, C
dc.contributor.authorWan, P
dc.contributor.authorSheng, X
dc.contributor.authorXia, L
dc.contributor.authorAndrews, C
dc.contributor.authorChen, F
dc.contributor.authorBerndt, SI
dc.contributor.authorKote-Jarai, Z
dc.contributor.authorGovindasami, K
dc.contributor.authorBensen, JT
dc.contributor.authorIngles, SA
dc.contributor.authorRybicki, BA
dc.contributor.authorNemesure, B
dc.contributor.authorJohn, EM
dc.contributor.authorFowke, JH
dc.contributor.authorHuff, CD
dc.contributor.authorStrom, SS
dc.contributor.authorIsaacs, WB
dc.contributor.authorPark, JY
dc.contributor.authorZheng, W
dc.contributor.authorOstrander, EA
dc.contributor.authorWalsh, PC
dc.contributor.authorCarpten, J
dc.contributor.authorSellers, TA
dc.contributor.authorYamoah, K
dc.contributor.authorMurphy, AB
dc.contributor.authorSanderson, M
dc.contributor.authorCrawford, DC
dc.contributor.authorGapstur, SM
dc.contributor.authorBush, WS
dc.contributor.authorAldrich, MC
dc.contributor.authorCussenot, O
dc.contributor.authorPetrovics, G
dc.contributor.authorCullen, J
dc.contributor.authorNeslund-Dudas, C
dc.contributor.authorKittles, RA
dc.contributor.authorXu, J
dc.contributor.authorStern, MC
dc.contributor.authorChokkalingam, AP
dc.contributor.authorMultigner, L
dc.contributor.authorParent, M-E
dc.contributor.authorMenegaux, F
dc.contributor.authorCancel-Tassin, G
dc.contributor.authorKibel, AS
dc.contributor.authorKlein, EA
dc.contributor.authorGoodman, PJ
dc.contributor.authorStanford, JL
dc.contributor.authorDrake, BF
dc.contributor.authorHu, JJ
dc.contributor.authorClark, PE
dc.contributor.authorBlanchet, P
dc.contributor.authorCasey, G
dc.contributor.authorHennis, AJM
dc.contributor.authorLubwama, A
dc.contributor.authorThompson, IM
dc.contributor.authorLeach, RJ
dc.contributor.authorGundell, SM
dc.contributor.authorPooler, L
dc.contributor.authorMohler, JL
dc.contributor.authorFontham, ETH
dc.contributor.authorSmith, GJ
dc.contributor.authorTaylor, JA
dc.contributor.authorBrureau, L
dc.contributor.authorBlot, WJ
dc.contributor.authorBiritwum, R
dc.contributor.authorTay, E
dc.contributor.authorTruelove, A
dc.contributor.authorNiwa, S
dc.contributor.authorTettey, Y
dc.contributor.authorVarma, R
dc.contributor.authorMcKean-Cowdin, R
dc.contributor.authorTorres, M
dc.contributor.authorJalloh, M
dc.contributor.authorMagueye Gueye, S
dc.contributor.authorNiang, L
dc.contributor.authorOgunbiyi, O
dc.contributor.authorOladimeji Idowu, M
dc.contributor.authorPopoola, O
dc.contributor.authorAdebiyi, AO
dc.contributor.authorAisuodionoe-Shadrach, OI
dc.contributor.authorNwegbu, M
dc.contributor.authorAdusei, B
dc.contributor.authorMante, S
dc.contributor.authorDarkwa-Abrahams, A
dc.contributor.authorYeboah, ED
dc.contributor.authorMensah, JE
dc.contributor.authorAnthony Adjei, A
dc.contributor.authorDiop, H
dc.contributor.authorCook, MB
dc.contributor.authorChanock, SJ
dc.contributor.authorWatya, S
dc.contributor.authorEeles, RA
dc.contributor.authorChiang, CWK
dc.contributor.authorLachance, J
dc.contributor.authorRebbeck, TR
dc.contributor.authorConti, DV
dc.contributor.authorHaiman, CA
dc.date.accessioned2022-04-01T10:42:47Z
dc.date.available2022-04-01T10:42:47Z
dc.date.issued2022-01-11
dc.identifier.citationEuropean urology, 2022en_US
dc.identifier.issn0302-2838
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5056
dc.identifier.eissn1873-7560en_US
dc.identifier.eissn1873-7560
dc.identifier.doi10.1016/j.eururo.2021.12.023en_US
dc.identifier.doi10.1016/j.eururo.2021.12.023
dc.description.abstractA rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0-0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10<sup>-4</sup>), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3-9.5, p = 2 × 10<sup>-5</sup>; stage T3/T4: OR = 4.5, 95% CI = 2.0-10.0, p = 2 × 10<sup>-4</sup>; metastatic disease: OR = 5.1, 95% CI = 1.9-13.7, p = 0.001). We estimated that the allele arose in West Africa 1500-4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. PATIENT SUMMARY: A rare African ancestry-specific germline deletion in HOXB13, found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry.en_US
dc.formatPrint-Electronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleA Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.en_US
dc.typeJournal Article
dcterms.dateAccepted2021-12-22
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/j.eururo.2021.12.023en_US
rioxxterms.licenseref.startdate2022-01-11
dc.relation.isPartOfEuropean urologyen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublisheden_US
pubs.embargo.termsNot knownen_US
icr.researchteamOncogenetics
dc.contributor.icrauthorEeles, Rosalinden_US
dc.contributor.icrauthorKote-Jarai, Zsofiaen_US


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