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dc.contributor.authorNyberg, Tommy
dc.contributor.authorGovindasami, Koveela
dc.contributor.authorLeslie, Goska
dc.contributor.authorDadaev, Tokhir
dc.contributor.authorBancroft, Elizabeth
dc.contributor.authorNi Raghallaigh, Holly
dc.contributor.authorBrook, Mark N
dc.contributor.authorHussain, Nafisa
dc.contributor.authorKeating, Diana
dc.contributor.authorLee, Andrew
dc.contributor.authorMcMahon, Romayne
dc.contributor.authorMorgan, Angela
dc.contributor.authorMullen, Andrea
dc.contributor.authorOsborne, Andrea
dc.contributor.authorRageevakumar, Reshma
dc.contributor.authorUK Genetic Prostate Cancer Study Collaborators
dc.contributor.authorKote-Jarai, Zsofia
dc.contributor.authorEeles, Rosalind
dc.contributor.authorAntoniou, Antonis
dc.date.accessioned2018-12-20T00:30:26Z
dc.date.available2018-12-20T00:30:26Z
dc.date.issued2019-05
dc.identifier.issn0302-2838
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287209
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.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectUK Genetic Prostate Cancer Study Collaborators
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectHomeodomain Proteins
dc.subjectMedical History Taking
dc.subjectRisk Assessment
dc.subjectRisk Factors
dc.subjectCohort Studies
dc.subjectAge Factors
dc.subjectMutation
dc.subjectMale
dc.subjectUnited Kingdom
dc.titleHomeobox B13 G84E Mutation and Prostate Cancer Risk.
dc.typeArticle
prism.endingPage845
prism.issueIdentifier5
prism.publicationDate2019
prism.publicationNameEur Urol
prism.startingPage834
prism.volume75
dc.identifier.doi10.17863/CAM.34516
dcterms.dateAccepted2018-11-08
rioxxterms.versionofrecord10.1016/j.eururo.2018.11.015
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-05
dc.contributor.orcidNyberg, Tommy [0000-0002-9436-0626]
dc.contributor.orcidLeslie, Goska [0000-0001-5756-6222]
dc.contributor.orcidLee, Andrew [0000-0003-0677-0252]
dc.contributor.orcidAntoniou, Antonis [0000-0001-9223-3116]
dc.identifier.eissn1873-7560
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (C12292/A22820)
pubs.funder-project-idCancer Research UK (20861)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International