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dc.contributor.authorNyberg, Ten_US
dc.contributor.authorGovindasami, Ken_US
dc.contributor.authorLeslie, Gen_US
dc.contributor.authorDadaev, Ten_US
dc.contributor.authorBancroft, Een_US
dc.contributor.authorNi Raghallaigh, Hen_US
dc.contributor.authorBrook, MNen_US
dc.contributor.authorHussain, Nen_US
dc.contributor.authorKeating, Den_US
dc.contributor.authorLee, Aen_US
dc.contributor.authorMcMahon, Ren_US
dc.contributor.authorMorgan, Aen_US
dc.contributor.authorMullen, Aen_US
dc.contributor.authorOsborne, Aen_US
dc.contributor.authorRageevakumar, Ren_US
dc.contributor.authorUK Genetic Prostate Cancer Study Collaboratorsen_US
dc.contributor.authorKote-Jarai, Zen_US
dc.contributor.authorEeles, Ren_US
dc.contributor.authorAntoniou, ACen_US
dc.coverage.spatialSwitzerlanden_US
dc.date.accessioned2018-12-21T12:12:34Z
dc.date.issued2019-05en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30527799en_US
dc.identifierS0302-2838(18)30872-8en_US
dc.identifier.citationEur Urol, 2019, 75 (5), pp. 834 - 845en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2983
dc.identifier.eissn1873-7560en_US
dc.identifier.doi10.1016/j.eururo.2018.11.015en_US
dc.description.abstractBACKGROUND: The homeobox B13 (HOXB13) G84E mutation has been recommended for use in genetic counselling for prostate cancer (PCa), but the magnitude of PCa risk conferred by this mutation is uncertain. OBJECTIVE: To obtain precise risk estimates for mutation carriers and information on how these vary by family history and other factors. DESIGN, SETTING, AND PARTICIPANTS: Two-fold: a systematic review and meta-analysis of published risk estimates, and a kin-cohort study comprising pedigree data on 11983 PCa patients enrolled during 1993-2014 from 189 UK hospitals and who had been genotyped for HOXB13 G84E. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relative and absolute PCa risks. Complex segregation analysis with ascertainment adjustment to derive age-specific risks applicable to the population, and to investigate how these vary by family history and birth cohort. RESULTS AND LIMITATIONS: A meta-analysis of case-control studies revealed significant heterogeneity between reported relative risks (RRs; range: 0.95-33.0, p<0.001) and differences by case selection (p=0.007). Based on case-control studies unselected for PCa family history, the pooled RR estimate was 3.43 (95% confidence interval [CI] 2.78-4.23). In the kin-cohort study, PCa risk for mutation carriers varied by family history (p<0.001). There was a suggestion that RRs decrease with age, but this was not significant (p=0.068). We found higher RR estimates for men from more recent birth cohorts (p=0.004): 3.09 (95% CI 2.03-4.71) for men born in 1929 or earlier and 5.96 (95% CI 4.01-8.88) for men born in 1930 or later. The absolute PCa risk by age 85 for a male HOXB13 G84E carrier varied from 60% for those with no PCa family history to 98% for those with two relatives diagnosed at young ages, compared with an average risk of 15% for noncarriers. Limitations include the reliance on self-reported cancer family history. CONCLUSIONS: PCa risks for HOXB13 G84E mutation carriers are heterogeneous. Counselling should not be based on average risk estimates but on age-specific absolute risk estimates tailored to individual mutation carriers' family history and birth cohort. PATIENT SUMMARY: Men who carry a hereditary mutation in the homeobox B13 (HOXB13) gene have a higher than average risk for developing prostate cancer. In our study, we examined a large number of families of men with prostate cancer recruited across UK hospitals, to assess what other factors may contribute to this risk and to assess whether we could create a precise model to help in predicting a man's prostate cancer risk. We found that the risk of developing prostate cancer in men who carry this genetic mutation is also affected by a family history of prostate cancer and their year of birth. This information can be used to assess more personalised prostate cancer risks to men who carry HOXB13 mutations and hence better counsel them on more personalised risk management options, such as tailoring prostate cancer screening frequency.en_US
dc.format.extent834 - 845en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectGenetic risken_US
dc.subjectHomeoboxB13en_US
dc.subjectKin-cohort studyen_US
dc.subjectMeta-analysisen_US
dc.subjectProstate canceren_US
dc.titleHomeobox B13 G84E Mutation and Prostate Cancer Risk.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-11-08en_US
rioxxterms.versionofrecord10.1016/j.eururo.2018.11.015en_US
rioxxterms.licenseref.startdate2019-05en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfEur Urolen_US
pubs.issue5en_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.volume75en_US
pubs.embargo.termsNot knownen_US
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorBrook, Marken_US
dc.contributor.icrauthorEeles, Rosalinden_US
dc.contributor.icrauthorKote-Jarai, Zsofiaen_US


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