Evidence map›Paper›PMID 29321194›Full record

ArticleBMJ (Clinical research ed.)2018

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

Tyler M Seibert, Chun Chieh Fan, Yunpeng Wang, Verena Zuber, Roshan Karunamuni, J Kellogg Parsons, Rosalind A Eeles, Douglas F Easton, ZSofia Kote-Jarai, Ali Amin Al Olama and 53 more

Registry-linked trialOpen access · hybridAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in BMJ (Clinical research ed.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04331535 (Pragmatic Randomized Trial of Polygenic Risk Scoring for Common Diseases in Primary Care), which is not on this map. Cited by 120 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 2 pooled it
21.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04331535 naunknown statusnot on this mapstarted 2020, after this paper: background citation

Pragmatic Randomized Trial of Polygenic Risk Scoring for Common Diseases in Primary Care

TypeinterventionalSponsorBoston VA Research Institute, Inc.Ran2020 to 2025Enrolled1,076ConditionsCoronary Artery Disease, Atrial Fibrillation, Type 2 Diabetes, Colorectal CancerArmsPolygenic risk score (PRS)
3 · Its place in the literature

Who cites it

120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 223 citations in OpenAlex.

  1. Pooled it
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  8. Polygenic risk scores in cancer.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
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  10. Germline polygenic score for prostate cancer aggressiveness.medRxiv : the preprint server for health sciences · 2026
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  13. Review
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60 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

63 authors at 20 institutions in 11 countries.

Tyler M SeibertCenter for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, USA tseibert@ucsd.edu amdale@ucsd.edu.
Chun Chieh FanCenter for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, USA.
Yunpeng WangNORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway.
Verena ZuberNORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway.
Roshan KarunamuniCenter for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, USA.
J Kellogg ParsonsDepartment of Surgery, University of California, San Diego, La Jolla, CA, USA.
Rosalind A EelesInstitute of Cancer Research, London, SM2 5NG, UK.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
ZSofia Kote-JaraiInstitute of Cancer Research, London, SM2 5NG, UK.
Ali Amin Al OlamaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
Sara Benlloch GarciaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
Kenneth MuirInstitute of Population Health, University of Manchester, Manchester, UK.
Henrik GrönbergDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Fredrik WiklundDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Markus AlyDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Johanna SchleutkerDepartment of Medical Biochemistry and Genetics, Institute of Biomedicine, Kiinamyllynkatu 10, FI-20014 University of Turku, Finland.
Csilla SipekyDepartment of Medical Biochemistry and Genetics, Institute of Biomedicine, Kiinamyllynkatu 10, FI-20014 University of Turku, Finland.
Teuvo Lj TammelaDepartment of Urology, Tampere University Hospital and Medical School, University of Tampere, Finland.
Børge G NordestgaardFaculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Sune F NielsenFaculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Maren WeischerDepartment of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Rasmus BisbjergDepartment of Urology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
M Andreas RøderCopenhagen Prostate Cancer Centre, Department of Urology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Peter IversenFaculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Tim J KeyCancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, Oxford OX3 7LF, UK.
Ruth C TravisCancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, Oxford OX3 7LF, UK.
David E NealNuffield Department of Surgical Sciences, Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Jenny L DonovanSchool of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.
Freddie C HamdyNuffield Department of Surgical Sciences, Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Paul PharoahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
Nora PashayanUniversity College London, Department of Applied Health Research, London WC1E 7HB, UK.
Kay-Tee KhawClinical Gerontology Unit, University of Cambridge, Cambridge UK.
Christiane MaierInstitute of Human Genetics, University Hospital of Ulm, Ulm, Germany.
Walther VogelInstitute of Human Genetics, University Hospital of Ulm, Ulm, Germany.
Manuel LuedekeInstitute of Human Genetics, University Hospital of Ulm, Ulm, Germany.
Kathleen HerkommerDepartment of Urology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany.
Adam S KibelDivision of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, 75 Francis Street, Boston, MA 02115, USA.
Cezary CybulskiInternational Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Dominika WokolorczykInternational Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Wojciech KluzniakInternational Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Lisa Cannon-AlbrightDivision of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Katarina CukDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Kai-Uwe SaumDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jong Y ParkDepartment of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Thomas A SellersOffice of the Center Director, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Chavdar SlavovDepartment of Urology and Alexandrovska University Hospital, Medical University, Sofia, Bulgaria.
Radka KanevaDepartment of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave Str, 1431 Sofia, Bulgaria.
Vanio MitevDepartment of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University, Sofia, 2 Zdrave Str, 1431 Sofia, Bulgaria.
Jyotsna BatraAustralian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Australia.
Judith A ClementsAustralian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Australia.
Amanda SpurdleMolecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
Manuel R TeixeiraDepartment of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Paula PauloDepartment of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Sofia MaiaDepartment of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Hardev PandhaUniversity of Surrey, Guildford, Surrey, GU2 7XH.
Agnieszka MichaelUniversity of Surrey, Guildford, Surrey, GU2 7XH.
Andrzej KierzekUniversity of Surrey, Guildford, Surrey, GU2 7XH.
David S KarowCenter for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, USA.
Ian G MillsNORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway.
Ole A AndreassenNORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway.
Anders M DaleCenter for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, USA tseibert@ucsd.edu amdale@ucsd.edu.
PRACTICAL Consortium*
University of California, San Diego · USUniversity of Cambridge · GBGentofte Hospital · DKKarolinska Institutet · SEUniversity Hospital Ulm · DEUniversity of Surrey · GBGerman Cancer Research Center · DEInstituto Português de Oncologia Francisco Gentil · PTMedical University of Sofia · BGMoffitt Cancer Center · USOslo University Hospital · NOPomeranian Medical University · PLQueensland University of Technology · AUUniversity of Oxford · GBAddenbrooke's Hospital · GBAlexandrovska Hospital · BGCopenhagen University Hospital · DKDana-Farber Brigham Cancer Center · USHeidelberg University · DEInstitute of Cancer Research · GB

Funding

Cancer Research UK 10118Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 13065Cancer Research UK 14136Cancer Research UK 15007Cancer Research UK 16491Cancer Research UK 16561Cancer Research UK 17528Cancer Research UK 19170Medical Research Council G0401527Medical Research Council G1000143Medical Research Council MC_UU_00002/7Medical Research Council MR/N003284/1Wellcome Trust 204623Wellcome Trust 204623/Z/16/Z
6 · The paper itself

Abstract

objectivesTo 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.

designAnalysis 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.

settingMultiple institutions that were members of international PRACTICAL consortium.

participantsAll consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men.

main outcome measuresPrediction with hazard score of age of onset of aggressive cancer in validation set.

resultsIn 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

conclusionsPolygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.

Indexed as

AgedAge of OnsetCohort StudiesDisease-Free SurvivalEarly Detection of CancerGenotypeHumansKallikreinsMaleMiddle AgedOutcome Assessment, Health CarePolymorphism, Single NucleotidePredictive Value of TestsProstate-Specific AntigenProstatic NeoplasmsRisk AssessmentKallikreinsKLK3 protein, humanProstate-Specific Antigen

Identifiers

PMID29321194
PMCPMC5759091
OpenAlexW2783014571

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.