Evidence map›Paper›PMID 41975491›Full record

ArticleJNCI cancer spectrum2026

Effect of a polygenic risk score in patients with late-onset, early-onset, familial, or hereditary colorectal cancer.

Hannah Klinkhammer, Isabel Spier, Claudia Perne, Per Hoffmann, Reinhard Büttner, Evelin Schröck, Silke Redler, Arne Jahn, Marcus Franke, Gabriela Möslein and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JNCI cancer spectrum, 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

22 authors.

Hannah KlinkhammerInstitute for Medical Biometry and Statistics, Philipps-University of Marburg, Marburg, Germany.ORCID 0000-0003-3752-1275
Isabel SpierInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Claudia PerneInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Per HoffmannInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Reinhard BüttnerInstitute of Pathology, Cologne University Hospital, Cologne, Germany.
Evelin SchröckInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.
Silke RedlerInstitute of Human Genetics, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Arne JahnInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.
Marcus FrankeInstitute for Clinical Genetics, University Hospital Carl Gustav Carus at TUD Dresden University of Technology and Faculty of Medicine of TUD Dresden University of Technology, Dresden, Germany.
Gabriela MösleinSurgical Center for Hereditary Tumors, BETHESDA Hospital Duisburg, Academic Hospital University of Düsseldorf, Duisburg, Germany.
Matthias KloorDepartment of Applied Tumor Biology, Heidelberg University Hospital, Heidelberg, Germany.
Börge SchmidtInstitute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Deepak VangalaOutpatient Center for Hematology and Oncology, Cancer Center Bochum-Herne, Bochum, Germany.
Huu Phuc NguyenDepartment of Human Genetics, Medical Faculty, Ruhr-University Bochum, Bochum, Germany.
Andreas J ForstnerInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.
Verena Steinke-LangeMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Elke Holinski-FederMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Robert HüneburgNational Center for Hereditary Tumour Syndromes, University Hospital Bonn, Bonn, Germany.
Carlo MajCentre for Human Genetics, University of Marburg, Marburg, Germany.
Christoph EngelInstitute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany.
Andreas MayrInstitute for Medical Biometry and Statistics, Philipps-University of Marburg, Marburg, Germany.
Stefan AretzInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany.ORCID 0000-0002-5228-1890

Funding

German Cancer Aid (Deutsche Krebshilfe) 107015German Cancer Aid (Deutsche Krebshilfe) 108913German Consortium Familial Intestinal Cancer (GC-FIC)Wellcome Trust 108445
6 · The paper itself

Abstract

objectiveThis study investigates how a polygenic risk score (PRS) influences colorectal cancer (CRC) risk across clinically and molecularly defined risk groups.

methodsIn total, 1839 European-descendant individuals were stratified according to low (<20%), intermediate (20% to 80%), or high (>80%) PRS, based on 93 CRC-associated single-nucleotide polymorphisms (SNPs), for 4 high-risk groups: (i) Lynch syndrome (LS; with CRC: n = 679, CRC-free carriers: n = 422); (ii) early-onset sporadic CRC (EOS-CRC; n = 518); (iii) positive family history for CRC (F-CRC; n = 220); and, in EOS-CRC and F-CRC patients, (iv) MSI/dMMR CRC (n = 144) vs MSS/pMMR CRC (n = 485). CRC risk was compared with population-based controls (n = 3119) and late-onset sporadic CRC patients from UK Biobank (LOS-CRC; n = 781) using multivariable logistic regression and Cox models.

resultsPolygenic risk score (PRS) was significantly increased in all risk groups compared with population controls. Being in the high PRS category doubled CRC risk in EOS-CRC and F-CRC corresponding to cumulative incidences before 50 and 75 years of 24% and 13%, respectively. Polygenic risk score was significantly higher in EOS-CRC than LOS-CRC. In LS, PRS in non-CRC carriers lay between CRC-LS and population controls. Non-LS individuals with MSI/dMMR tumors showed significantly lower PRS than those with pMMR/MSS tumors, but no difference compared with LS CRC individuals.

conclusionsPolygenic risk score most strongly influences CRC risk in unexplained EOS- and F-CRC. The effect in LS individuals strongly depends on the penetrance of the altered gene and study design. Nonsignificant trends can partly be explained by the sample size of subgroups. Larger collaborative, prospective studies are needed to validate PRS for personalized CRC risk stratification.

Indexed as

Colorectal NeoplasmsGenetic Risk ScoreMultifactorial InheritanceAdultAgedAge of OnsetCase-Control StudiesColorectal Neoplasms, Hereditary NonpolyposisFemaleHumansLogistic ModelsMaleMicrosatellite InstabilityMiddle AgedPolymorphism, Single NucleotideProportional Hazards Models

Identifiers

PMID41975491
PMCPMC13263116

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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.