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dc.contributor.authorNyberg, Tommyen
dc.contributor.authorFrost, Debraen
dc.contributor.authorBarrowdale, Danielen
dc.contributor.authorEvans, D Garethen
dc.contributor.authorBancroft, Elizabethen
dc.contributor.authorAdlard, Julianen
dc.contributor.authorAhmed, Munazaen
dc.contributor.authorBarwell, Julianen
dc.contributor.authorBrady, Angela Fen
dc.contributor.authorBrewer, Caroleen
dc.contributor.authorCook, Jackieen
dc.contributor.authorDavidson, Rosemarieen
dc.contributor.authorDonaldson, Alanen
dc.contributor.authorEason, Jacquelineen
dc.contributor.authorGregory, Helenen
dc.contributor.authorHenderson, Alexen
dc.contributor.authorIzatt, Louiseen
dc.contributor.authorKennedy, M Johnen
dc.contributor.authorMiller, Claireen
dc.contributor.authorMorrison, Patrick Jen
dc.contributor.authorMurray, Alexen
dc.contributor.authorOng, Kai-Renen
dc.contributor.authorPorteous, Maryen
dc.contributor.authorPottinger, Carolineen
dc.contributor.authorRogers, Mark Ten
dc.contributor.authorSide, Lucyen
dc.contributor.authorSnape, Katieen
dc.contributor.authorWalker, Lisaen
dc.contributor.authorTischkowitz, Marcen
dc.contributor.authorEeles, Rosalinden
dc.contributor.authorEaston, Douglasen
dc.contributor.authorAntoniou, Antonisen
dc.date.accessioned2019-08-28T23:30:12Z
dc.date.available2019-08-28T23:30:12Z
dc.date.issued2019-09-05en
dc.identifier.issn0302-2838
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/296207
dc.description.abstractBACKGROUND BRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of risk estimates has been reported, based on retrospective studies. OBJECTIVE To estimate relative and absolute PCa risks associated with BRCA1/2 mutations, and to assess risk-modification by age, family history and mutation location. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of male BRCA1 (n=376) and BRCA2 carriers (n=447) identified through clinical genetics centres in the UK and Republic of Ireland (median follow-up: 5.9 and 5.3 yr, respectively). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Standardised incidence/mortality ratios (SIRs/SMRs) relative to population incidences or mortality rates, absolute risks and hazard ratios (HRs), estimated using cohort and survival analysis methods. RESULTS AND LIMITATIONS Sixteen BRCA1 and 26 BRCA2 carriers were diagnosed with PCa during follow-up. BRCA2 carriers had a SIR of 4.45 (95% confidence interval [CI] 2.99-6.61), and absolute PCa risk of 27% (95% CI 17%-41%) and 60% (95% CI 43%-78%) by ages 75 and 85, respectively. For BRCA1 carriers, the overall SIR was 2.35 (95% CI 1.43-3.88); the corresponding SIR at ages<65 was 3.57 (95% CI 1.68-7.58). However, the BRCA1 SIR varied between 0.74 and 2.83 in sensitivity analyses to assess potential screening effects. PCa risks for BRCA2 carriers increased with family history (HR per affected relative=1.68, 95% CI 0.99-2.85). BRCA2 mutations in the region bounded by positions c.2831–c.6401 were associated with an SIR of 2.46 (95% CI 1.07-5.64) compared to population incidences, corresponding to a lower PCa risk (HR=0.37, 95% CI 0.14-0.96) than for mutations outside the region. BRCA2 carriers had a stronger association with Gleason score≥7 (SIR=5.07, 95% CI 3.20-8.02) than Gleason score≤6 PCa (SIR=3.03, 95% CI 1.24-7.44), and increased risk of death from PCa (SMR=3.85, 95% CI 1.44-10.3). Limitations include potential screening effects for these known mutation carriers; however, the BRCA2 results were robust to multiple sensitivity analyses. CONCLUSIONS The results substantiate PCa risk patterns indicated by retrospective analyses for BRCA2 carriers, including further evidence of association with aggressive PCa, and give some support for a weaker association in BRCA1 carriers.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleProstate Cancer Risks for Male BRCA1 and BRCA2 Mutation Carriers: A Prospective Cohort Study.en
dc.typeArticle
prism.publicationDate2019en
prism.publicationNameEuropean urologyen
dc.identifier.doi10.17863/CAM.43252
dcterms.dateAccepted2019-08-15en
rioxxterms.versionofrecord10.1016/j.eururo.2019.08.025en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-09-05en
dc.contributor.orcidNyberg, Tommy [0000-0002-9436-0626]
dc.contributor.orcidTischkowitz, Marc [0000-0002-7880-0628]
dc.contributor.orcidEeles, Rosalind [0000-0002-3698-6241]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.contributor.orcidAntoniou, Antonis [0000-0001-9223-3116]
dc.identifier.eissn1873-7560
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (C12292/A20861)
pubs.funder-project-idCancer Research UK (C12292/A22820)
pubs.funder-project-idCancer Research UK (A23382)
rioxxterms.freetoread.startdate2022-08-28


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Attribution-NonCommercial-NoDerivatives 4.0 International
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