Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts
dc.date.accessioned | 2018-09-06T12:26:04Z | |
dc.date.available | 2018-09-06T12:26:04Z | |
dc.date.created | 2018-02-01T10:44:46Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Seibert, 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.uri | http://hdl.handle.net/10852/64169 | |
dc.description.abstract | Objectives: 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.language | EN | |
dc.publisher | BMJ Publishing Group | |
dc.rights | Attribution-NonCommercial 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.title | Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Seibert, TM | |
dc.creator.author | Fan, CC | |
dc.creator.author | Wang, Yan | |
dc.creator.author | Zuber, W | |
dc.creator.author | Karunamuni, R | |
dc.creator.author | Parsons, JK | |
dc.creator.author | Eeles, RA | |
dc.creator.author | Easton, DF | |
dc.creator.author | Kote-Jarai, Z | |
dc.creator.author | Al Olama, Ali Amin | |
dc.creator.author | Garcia, SB | |
dc.creator.author | Muir, K | |
dc.creator.author | Gronberg, Henrik | |
dc.creator.author | Wiklund, Fredrik | |
dc.creator.author | Aly, Markus | |
dc.creator.author | Schleutker, Johanna | |
dc.creator.author | Sipeki, C | |
dc.creator.author | Tammela, TM | |
dc.creator.author | Nordestgaard, BG | |
dc.creator.author | Nielsen, SF | |
dc.creator.author | Weischer, Maren | |
dc.creator.author | Bisbjerg, R | |
dc.creator.author | Røder, MA | |
dc.creator.author | Iversen, P | |
dc.creator.author | Key, TJ | |
dc.creator.author | Travis, RC | |
dc.creator.author | Neal, DE | |
dc.creator.author | Donovan, JL | |
dc.creator.author | Hamdy, FC | |
dc.creator.author | Pharaoa, P | |
dc.creator.author | Pashayan, Nora | |
dc.creator.author | Khaw, KT | |
dc.creator.author | Maier, C. | |
dc.creator.author | Vogel, Walther | |
dc.creator.author | Luedeke, M | |
dc.creator.author | Herkommer, K | |
dc.creator.author | Kibel, AS | |
dc.creator.author | Cybulski, C | |
dc.creator.author | Vokolorzcyk, D | |
dc.creator.author | Klusniak, W | |
dc.creator.author | Cannon-Albright, D | |
dc.creator.author | Brenner, H. | |
dc.creator.author | Cuk, K | |
dc.creator.author | Saum, KU | |
dc.creator.author | Park, JY | |
dc.creator.author | Sellers, TA | |
dc.creator.author | Slavov, C | |
dc.creator.author | Kaneva, R | |
dc.creator.author | Mitev, V | |
dc.creator.author | Batra, J | |
dc.creator.author | Clements, JA | |
dc.creator.author | Spurdle, A | |
dc.creator.author | Teixeira, MR | |
dc.creator.author | Paulo, P | |
dc.creator.author | Maia, S | |
dc.creator.author | Phanda, H | |
dc.creator.author | Michael, A | |
dc.creator.author | Kierzek, A | |
dc.creator.author | Karow, DS | |
dc.creator.author | Mills, Ian Geoffrey | |
dc.creator.author | Andreassen, Ole Andreas | |
dc.creator.author | Dale, AM | |
cristin.unitcode | 185,53,10,70 | |
cristin.unitname | NORMENT part UiO | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1560343 | |
dc.identifier.bibliographiccitation | info: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.jtitle | BMJ Open | |
dc.identifier.volume | 360 | |
dc.identifier.doi | http://dx.doi.org/10.1136/bmj.j5757. | |
dc.identifier.urn | URN:NBN:no-66725 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2044-6055 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/64169/4/bmj.j5757.full.pdf | |
dc.type.version | PublishedVersion | |
dc.relation.project | NFR/144182 |
Files in this item
Appears in the following Collection
-
Det medisinske fakultet [556]
-
CRIStin høstingsarkiv [30840]