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dc.date.accessioned2018-09-06T12:26:04Z
dc.date.available2018-09-06T12:26:04Z
dc.date.created2018-02-01T10:44:46Z
dc.date.issued2018
dc.identifier.citationSeibert, TM Fan, CC Wang, Yan Zuber, W Karunamuni, R Parsons, JK Eeles, RA Easton, DF Kote-Jarai, Z Al Olama, Ali Amin Garcia, SB Muir, K Gronberg, Henrik Wiklund, Fredrik Aly, Markus Schleutker, Johanna Sipeki, C Tammela, TM Nordestgaard, BG Nielsen, SF Weischer, Maren Bisbjerg, R Røder, MA Iversen, P Key, TJ Travis, RC Neal, DE Donovan, JL Hamdy, FC Pharaoa, P Pashayan, Nora Khaw, KT Maier, C. Vogel, Walther Luedeke, M Herkommer, K Kibel, AS Cybulski, C Vokolorzcyk, D Klusniak, W Cannon-Albright, D Brenner, H. Cuk, K Saum, KU Park, JY Sellers, TA Slavov, C Kaneva, R Mitev, V Batra, J Clements, JA Spurdle, A Teixeira, MR Paulo, P Maia, S Phanda, H Michael, A Kierzek, A Karow, DS Mills, Ian Geoffrey Andreassen, Ole Andreas Dale, AM . Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts. BMJ Open. 2018, 360
dc.identifier.urihttp://hdl.handle.net/10852/64169
dc.description.abstractObjectives: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. Design: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. Results: In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10−16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. Conclusions: Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.en_US
dc.languageEN
dc.publisherBMJ Publishing Group
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.titlePolygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohortsen_US
dc.typeJournal articleen_US
dc.creator.authorSeibert, TM
dc.creator.authorFan, CC
dc.creator.authorWang, Yan
dc.creator.authorZuber, W
dc.creator.authorKarunamuni, R
dc.creator.authorParsons, JK
dc.creator.authorEeles, RA
dc.creator.authorEaston, DF
dc.creator.authorKote-Jarai, Z
dc.creator.authorAl Olama, Ali Amin
dc.creator.authorGarcia, SB
dc.creator.authorMuir, K
dc.creator.authorGronberg, Henrik
dc.creator.authorWiklund, Fredrik
dc.creator.authorAly, Markus
dc.creator.authorSchleutker, Johanna
dc.creator.authorSipeki, C
dc.creator.authorTammela, TM
dc.creator.authorNordestgaard, BG
dc.creator.authorNielsen, SF
dc.creator.authorWeischer, Maren
dc.creator.authorBisbjerg, R
dc.creator.authorRøder, MA
dc.creator.authorIversen, P
dc.creator.authorKey, TJ
dc.creator.authorTravis, RC
dc.creator.authorNeal, DE
dc.creator.authorDonovan, JL
dc.creator.authorHamdy, FC
dc.creator.authorPharaoa, P
dc.creator.authorPashayan, Nora
dc.creator.authorKhaw, KT
dc.creator.authorMaier, C.
dc.creator.authorVogel, Walther
dc.creator.authorLuedeke, M
dc.creator.authorHerkommer, K
dc.creator.authorKibel, AS
dc.creator.authorCybulski, C
dc.creator.authorVokolorzcyk, D
dc.creator.authorKlusniak, W
dc.creator.authorCannon-Albright, D
dc.creator.authorBrenner, H.
dc.creator.authorCuk, K
dc.creator.authorSaum, KU
dc.creator.authorPark, JY
dc.creator.authorSellers, TA
dc.creator.authorSlavov, C
dc.creator.authorKaneva, R
dc.creator.authorMitev, V
dc.creator.authorBatra, J
dc.creator.authorClements, JA
dc.creator.authorSpurdle, A
dc.creator.authorTeixeira, MR
dc.creator.authorPaulo, P
dc.creator.authorMaia, S
dc.creator.authorPhanda, H
dc.creator.authorMichael, A
dc.creator.authorKierzek, A
dc.creator.authorKarow, DS
dc.creator.authorMills, Ian Geoffrey
dc.creator.authorAndreassen, Ole Andreas
dc.creator.authorDale, AM
cristin.unitcode185,53,10,70
cristin.unitnameNORMENT part UiO
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1560343
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=BMJ Open&rft.volume=360&rft.spage=&rft.date=2018
dc.identifier.jtitleBMJ Open
dc.identifier.volume360
dc.identifier.doihttp://dx.doi.org/10.1136/bmj.j5757.
dc.identifier.urnURN:NBN:no-66725
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn2044-6055
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/64169/4/bmj.j5757.full.pdf
dc.type.versionPublishedVersion
dc.relation.projectNFR/144182


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