Evidence map›Paper›PMID 42204244›Full record

ArticleCommunications medicine2026

Polygenic risk score with KLK3 SNP-SNP interaction pairs for predicting prostate cancer aggressiveness.

Hui-Yi Lin, Indrani Sarkar, Harun Mazumder, Po-Yu Huang, Kenneth R Muir, Johanna Schleutker, Nora Pashayan, Jyotsna Batra, David E Neal, Henrik Grönberg and 44 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

54 authors.

Hui-Yi LinBiostatistics and Data Science Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA. hlin1@lsuhsc.edu.ORCID http://orcid.org/0000-0002-3307-5549
Indrani SarkarBiostatistics and Data Science Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.ORCID http://orcid.org/0009-0004-1545-6470
Harun MazumderBiostatistics and Data Science Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Po-Yu HuangInformation and Communications Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
Kenneth R MuirDivision of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester, UK.ORCID http://orcid.org/0000-0001-6429-988X
Johanna SchleutkerInstitute of Biomedicine, University of Turku, Turku, Finland.ORCID http://orcid.org/0000-0002-1863-0305
Nora PashayanDepartment of Public Health & Primary Care, Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.ORCID http://orcid.org/0000-0003-0843-2468
Jyotsna BatraSchool of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0003-4646-6247
David E NealNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Henrik GrönbergDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-1073-2753
Sune F NielsenDepartment of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.ORCID http://orcid.org/0000-0002-3509-9560
Børge G NordestgaardDepartment of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.ORCID http://orcid.org/0000-0002-1954-7220
Catherine M TangenSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Robert J MacInnisCancer Epidemiology Division, Cancer Council Victoria, East Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-1627-5047
Alicja WolkInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-7387-6845
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8330-4293
Ruth C TravisCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9571-0763
Janet L StanfordDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lorelei A MucciDepartment of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Adam S KibelDivision of Urologic Surgery, Brigham and Women's Hospital, Boston, MA, USA.
Olivier CussenotSorbonne Universite, Tenon Hospital, Paris, France.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
Stella KoutrosDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
Karina Dalsgaard SørensenDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark.ORCID http://orcid.org/0000-0002-4902-5490
Cezary CybulskiInternational Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Eli Marie GrindedalDepartment of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Josef HoegelInstitute for Human Genetics, University Hospital Ulm, Ulm, Germany.
Christiane MaierHumangenetik Tuebingen, Tuebingen, Germany.
Robert J HamiltonDept. of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Barry S RosensteinDepartment of Radiation Oncology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ana VegaFundación Pública Galega Medicina Xenómica, Santiago de Compostela, Spain.ORCID http://orcid.org/0000-0002-7416-5137
Manolis KogevinasISGlobal, Barcelona, Spain.
Fredrik WiklundDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-4623-0544
Kathryn L PenneyChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
Manuel R TeixeiraDepartment of Laboratory Genetics, Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center, Porto, Portugal.ORCID http://orcid.org/0000-0002-4896-5982
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-6129-1572
Esther M JohnDepartments of Epidemiology & Population Health and of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Radka KanevaMolecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, Bulgaria.ORCID http://orcid.org/0000-0002-1437-1393
Christopher J LogothetisThe University of Texas M. D. Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, TX, USA.ORCID http://orcid.org/0000-0002-6365-1711
Susan L NeuhausenDepartment of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, USA.ORCID http://orcid.org/0000-0001-5053-0390
Kim De RuyckGhent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences, Gent, Belgium.
Piet OstDepartment of Radiotherapy, Ghent University Hospital, Gent, Belgium.ORCID http://orcid.org/0000-0002-2203-4848
Marija GamulinDepartment of Oncology, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, Zagreb, Croatia.ORCID http://orcid.org/0000-0003-2431-7910
Nawaid UsmaniDepartment of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
Frank ClaessensDepartment of Cellular and Molecular Medicine, Molecular Endocrinology Laboratory, KU Leuven, Belgium.
Jose Esteban CastelaoGenetic Oncology Unit, CHUVI Hospital, Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomédica Galicia Sur (IISGS), Vigo (Pontevedra), Spain.
Paul A TownsendDivision of Cancer Sciences, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Health Innovation Manchester, University of Manchester, Manchester, UK.
UKGPCS collaborators
APCB BioResource (Australian Prostate Cancer BioResource)
Zsofia Kote-JaraiThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-6329-5155
Christopher A HaimanCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Rosalind A EelesThe Institute of Cancer Research, London, UK.ORCID http://orcid.org/0000-0002-3698-6241
PRACTICAL consortium
Jong Y ParkDepartment of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.ORCID http://orcid.org/0000-0002-6384-6447

Funding

U.S. Department of Defense (United States Department of Defense) HT9425-23-1-0438
6 · The paper itself

Abstract

backgroundProstate cancer (PCa) is heterogeneous, making risk stratification essential for clinical care. Although polygenic risk scores (PRSs) with main effects of single-nucleotide polymorphisms (SNPs) can help identify individuals at high risk before biological and clinical onset, a PRS for predicting PCa aggressiveness remains underdeveloped. The KLK3, which encodes prostate-specific antigen (PSA), is linked to PCa aggressiveness. Recent findings on KLK3 SNP-SNP interactions show promise for predicting PCa aggressiveness. The objective of this study is to develop a PRS (PRS-KLK3int) by examining KLK3 SNP-SNP interaction pairs.

methodsThe PRS-KLK3int was developed based on a discovery set (10,836 PCa patients) and two validation sets with 14,348 and 16,584 patients of European ancestry. A total of 3145 SNP pairs and two published PRSs were evaluated.

resultsThis study developed a PRS-KLK3int with 284 SNPs, combining an existing PRS with 270 SNPs and 12 SNP-SNP interaction pairs with 15 SNPs (one overlapped). All these 12 pairs were involved with at least one SNP from KLK3. The PRS-KLK3int outperformed two existing PRSs in predicting PCa aggressiveness (p-values: 3.5×10

conclusionsThese findings support PRS-KLK3int as a valuable tool for PCa severity stratification, especially in identifying extremely high-risk PCa patients.

Identifiers

PMID42204244
PMCPMC13493922

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.