dc.contributor.author | Karunamuni, RA | |
dc.contributor.author | Huynh-Le, M-P | |
dc.contributor.author | Fan, CC | |
dc.contributor.author | Thompson, W | |
dc.contributor.author | Eeles, RA | |
dc.contributor.author | Kote-Jarai, Z | |
dc.contributor.author | Muir, K | |
dc.contributor.author | Lophatananon, A | |
dc.contributor.author | UKGPCS collaborators, | |
dc.contributor.author | Schleutker, J | |
dc.contributor.author | Pashayan, N | |
dc.contributor.author | Batra, J | |
dc.contributor.author | APCB BioResource (Australian Prostate Cancer BioResource), | |
dc.contributor.author | Grönberg, H | |
dc.contributor.author | Walsh, EI | |
dc.contributor.author | Turner, EL | |
dc.contributor.author | Lane, A | |
dc.contributor.author | Martin, RM | |
dc.contributor.author | Neal, DE | |
dc.contributor.author | Donovan, JL | |
dc.contributor.author | Hamdy, FC | |
dc.contributor.author | Nordestgaard, BG | |
dc.contributor.author | Tangen, CM | |
dc.contributor.author | MacInnis, RJ | |
dc.contributor.author | Wolk, A | |
dc.contributor.author | Albanes, D | |
dc.contributor.author | Haiman, CA | |
dc.contributor.author | Travis, RC | |
dc.contributor.author | Stanford, JL | |
dc.contributor.author | Mucci, LA | |
dc.contributor.author | West, CML | |
dc.contributor.author | Nielsen, SF | |
dc.contributor.author | Kibel, AS | |
dc.contributor.author | Wiklund, F | |
dc.contributor.author | Cussenot, O | |
dc.contributor.author | Berndt, SI | |
dc.contributor.author | Koutros, S | |
dc.contributor.author | Sørensen, KD | |
dc.contributor.author | Cybulski, C | |
dc.contributor.author | Grindedal, EM | |
dc.contributor.author | Park, JY | |
dc.contributor.author | Ingles, SA | |
dc.contributor.author | Maier, C | |
dc.contributor.author | Hamilton, RJ | |
dc.contributor.author | Rosenstein, BS | |
dc.contributor.author | Vega, A | |
dc.contributor.author | IMPACT Study Steering Committee and Collaborators, | |
dc.contributor.author | Kogevinas, M | |
dc.contributor.author | Penney, KL | |
dc.contributor.author | Teixeira, MR | |
dc.contributor.author | Brenner, H | |
dc.contributor.author | John, EM | |
dc.contributor.author | Kaneva, R | |
dc.contributor.author | Logothetis, CJ | |
dc.contributor.author | Neuhausen, SL | |
dc.contributor.author | Razack, A | |
dc.contributor.author | Newcomb, LF | |
dc.contributor.author | Canary PASS Investigators, | |
dc.contributor.author | Gamulin, M | |
dc.contributor.author | Usmani, N | |
dc.contributor.author | Claessens, F | |
dc.contributor.author | Gago-Dominguez, M | |
dc.contributor.author | Townsend, PA | |
dc.contributor.author | Roobol, MJ | |
dc.contributor.author | Zheng, W | |
dc.contributor.author | Profile Study Steering Committee, | |
dc.contributor.author | Mills, IG | |
dc.contributor.author | Andreassen, OA | |
dc.contributor.author | Dale, AM | |
dc.contributor.author | Seibert, TM | |
dc.contributor.author | PRACTICAL Consortium, | |
dc.date.accessioned | 2022-01-25T11:24:11Z | |
dc.date.available | 2022-01-25T11:24:11Z | |
dc.date.issued | 2021-01-08 | |
dc.identifier.citation | Prostate cancer and prostatic diseases, 2021 | |
dc.identifier.issn | 1365-7852 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4968 | |
dc.identifier.eissn | 1476-5608 | |
dc.identifier.eissn | 1476-5608 | |
dc.identifier.doi | 10.1038/s41391-020-00311-2 | |
dc.identifier.doi | 10.1038/s41391-020-00311-2 | |
dc.description.abstract | BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGERNATURE | |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | UKGPCS collaborators | |
dc.subject | APCB BioResource (Australian Prostate Cancer BioResource) | |
dc.subject | IMPACT Study Steering Committee and Collaborators | |
dc.subject | Canary PASS Investigators | |
dc.subject | Profile Study Steering Committee | |
dc.subject | PRACTICAL Consortium | |
dc.title | Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-12-04 | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1038/s41391-020-00311-2 | |
rioxxterms.licenseref.startdate | 2021-01-08 | |
dc.relation.isPartOf | Prostate cancer and prostatic diseases | |
pubs.notes | Not known | |
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-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Eeles, Rosalind | |
dc.contributor.icrauthor | Kote-Jarai, Zsofia | |