Evidence map›Paper›PMID 34203177›Full record

ArticleJournal of clinical medicine2021

No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in

Mev Dominguez-Valentin, John-Paul Plazzer, Julian R Sampson, Christoph Engel, Stefan Aretz, Mark A Jenkins, Lone Sunde, Inge Bernstein, Gabriel Capella, Francesc Balaguer and 79 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.6field-weighted citation impact, top 10% 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.

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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
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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

89 authors at 20 institutions in 17 countries.

Mev Dominguez-ValentinDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.ORCID 0000-0001-7856-0057
John-Paul PlazzerThe International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.ORCID 0000-0001-5114-4301
Julian R SampsonEuropean Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
Christoph EngelEuropean Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.ORCID 0000-0002-7247-282X
Stefan AretzInstitute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.ORCID 0000-0002-5228-1890
Mark A JenkinsMelbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC 3010, Australia.
Lone SundeDepartment of Clinical Genetics, Aalborg University Hospital, 9000 Aalborg, Denmark.
Inge BernsteinDepartment of Surgical Gastroenterology, Aalborg University Hospital, Aalborg University, 9100 Aalborg, Denmark.
Gabriel CapellaEuropean Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.ORCID 0000-0002-4669-7320
Francesc BalaguerGastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain.ORCID 0000-0002-0206-0539
Finlay MacraeThe International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Ingrid M WinshipDepartment of Genomic Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3052, Australia.
Huw ThomasDepartment of Surgery and Cancer, St Mark's Hospital, Imperial College London, London HA1 3UJ, UK.
Dafydd Gareth EvansManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.ORCID 0000-0002-8482-5784
John BurnEuropean Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.ORCID 0000-0002-9823-2322
Marc GreenblattLarner College of Medicine, University of Vermont, Burlington, VT 05405, USA.
Wouter H de Vos Tot Nederveen CappelDepartment of Gastroenterology and Hepatology, Isala Clinics, 8015 Zwolle, The Netherlands.ORCID 0000-0002-3956-1206
Rolf H SijmonsEuropean Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
Maartje NielsenDepartment of Clinical Genetics, Leids Universitair Medisch Centrum, 2300RC Leiden, The Netherlands.ORCID 0000-0002-5351-1870
Lucio BertarioDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, IRCCS, 20141 Milan, Italy.
Bernardo BonanniDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, 20141 Milan, Italy.ORCID 0000-0003-3589-2128
Maria Grazia TibilettiOspedale di Circolo ASST Settelaghi, Centro di Ricerca Tumori Eredo-Familiari, Università dell'Insubria, 21100 Varese, Italy.
Giulia Martina CavestroGastroenterology and Gastrointestinal Endoscopy Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy.
Annika LindblomDepartment of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden.
Adriana Della ValleGrupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Hospital Fuerzas Armadas, Montevideo 11600, Uruguay.
Francisco Lopez-KostnerPrograma Cáncer Heredo Familiar, Clínica Universidad de los Andes, Santiago 7550000, Chile.
Karin AlvarezPrograma Cáncer Heredo Familiar, Clínica Universidad de los Andes, Santiago 7550000, Chile.
Nathan GluckDepartment of Gastroenterology, Sackler Faculty of Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv 64259, Israel.ORCID 0000-0001-5503-488X
Lior KatzThe Department of Gastroenterology, Gastro-Oncology Unit, High Risk and GI Cancer Prevention Clinic, Sheba Medical Center, Sheba 91120, Israel.
Karl HeinimannMedical Genetics, Institute for Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, Switzerland.
Carlos A VaccaroHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.ORCID 0000-0002-1299-5864
Sigve NakkenDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.ORCID 0000-0001-8468-2050
Eivind HovigDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.ORCID 0000-0002-9103-1077
Kate GreenManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
Fiona LallooManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
James HillDepartment of Surgery, Central Manchester University Hospitals NHS, Foundation Trust, University of Manchester, London M13 9WL, UK.
Hans F A VasenDepartment of Gastroenterology and Hepatology, Leiden University Medical Centre, 2333 Leiden, The Netherlands.
Claudia PerneInstitute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
Reinhard BüttnerInstitute of Pathology, University of Cologne, 50937 Cologne, Germany.
Heike GörgensDepartment of Surgery, Technische Universität Dresden, 01062 Dresden, Germany.
Elke Holinski-FederThe International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Monika MorakCampus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.
Stefanie HolzapfelInstitute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
Robert HüneburgDepartment of Internal Medicine, University Hospital Bonn, 53127 Bonn, Germany.ORCID 0000-0001-9957-8299
Magnus von Knebel DoeberitzDepartment of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Markus LoefflerInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany.
Nils RahnerMedical School, Institute of Human Genetics, Heinrich-Heine-University, 40225 Dusseldorf, Germany.
Jürgen WeitzDepartment of Surgery, Technische Universität Dresden, 01062 Dresden, Germany.
Verena Steinke-LangeCampus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.ORCID 0000-0001-8491-3234
Wolff SchmiegelDepartment of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, D-44789 Bochum, Germany.
Deepak VangalaDepartment of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, D-44789 Bochum, Germany.ORCID 0000-0002-4175-5683
Emma J CrosbieGynaecological Oncology Research Group, Manchester University NHS Foundation Trust, Manchester, UK and Division of Cancer Sciences, University of Manchester, Manchester M20 4GJ, UK.ORCID 0000-0003-0284-8630
Marta PinedaHereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L, Hospitalet de Llobregat, 08908 Barcelona, Spain.ORCID 0000-0002-5403-5845
Matilde NavarroHereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L, Hospitalet de Llobregat, 08908 Barcelona, Spain.
Joan BrunetHereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L, Hospitalet de Llobregat, 08908 Barcelona, Spain.ORCID 0000-0003-1945-3512
Leticia MoreiraGastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain.ORCID 0000-0002-4518-8591
Ariadna SánchezGastroenterology Department, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain.ORCID 0000-0003-0409-1328
Miquel Serra-BurrielCentre de Recerca en Economia i Salut (CRES-UPF), Universitat de Barcelona, 08002 Barcelona, Spain.
Miriam MintsDivision of Obstetrics and Gyneacology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Solna, 171 77 Stockholm, Sweden.
Revital KarivDepartment of Gastroenterology, Sackler Faculty of Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv 64259, Israel.
Guy RosnerDepartment of Gastroenterology, Sackler Faculty of Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv 64259, Israel.
Tamara Alejandra PiñeroHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.
Walter Hernán PavicicHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.ORCID 0000-0001-7840-4943
Pablo KalfayanHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.
Sanne W Ten BroekeDepartment of Clinical Genetics, Leids Universitair Medisch Centrum, 2300RC Leiden, The Netherlands.ORCID 0000-0001-6280-0087
Jukka-Pekka MecklinEuropean Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
Kirsi PylvänäinenDepartment of Education and Science, Sport and Health Sciences, Central Finland Hospital Nova, University of Jyväskylä, FI-40014 Jyväskylä, Finland.ORCID 0000-0003-4399-9283
Laura Renkonen-SinisaloApplied Tumour Genomics Research Program, University of Helsinki, 00014 Helsinki, Finland.
Anna LepistöApplied Tumour Genomics Research Program, University of Helsinki, 00014 Helsinki, Finland.
Päivi PeltomäkiDepartment of Medical and Clinical Genetics, University of Helsinki, 00014 Helsinki, Finland.
John L HopperMelbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC 3010, Australia.
Aung Ko WinMelbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC 3010, Australia.ORCID 0000-0002-2794-5261
Daniel D BuchananCentre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3010, Australia.ORCID 0000-0003-2225-6675
Noralane M LindorDepartment of Health Science Research, Mayo Clinic Arizona, Phoenix, AZ 85054, USA.
Steven GallingerLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON M5G 1X5, Canada.
Loïc Le MarchandCancer Center, University of Hawaii, Honolulu, HI 96813, USA.ORCID 0000-0001-5013-980X
Polly A NewcombPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Jane C FigueiredoCedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Stephen N ThibodeauDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Christina TherkildsenThe Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, 2560 Hvidovre, Denmark.
Thomas V O HansenDepartment of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.
Lars LindbergGastro Unit, Copenhagen University Hospital, 2560 Hvidovre, Denmark.
Einar Andreas RødlandDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.ORCID 0000-0002-9780-8385
Florencia NeffaGrupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Hospital Fuerzas Armadas, Montevideo 11600, Uruguay.
Patricia EsperonGrupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Hospital Fuerzas Armadas, Montevideo 11600, Uruguay.ORCID 0000-0002-3080-5702
Douglas TjandraDepartment of Medicine, Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.ORCID 0000-0002-2236-5225
Gabriela MösleinEuropean Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
Toni T SeppäläEuropean Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.ORCID 0000-0002-4940-3498
Pål MøllerDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.
Manchester University NHS Foundation Trust · GBThe Royal Melbourne Hospital · AUInstitut d'Investigació Biomédica de Bellvitge · ESUniversity of Helsinki · FIConsejo Nacional de Investigaciones Científicas y Técnicas · ARCopenhagen University Hospital · DKHospital Central de las Fuerzas Armadas · UYHospital Clínic de Barcelona · ESLMU Klinikum · DENorwegian Cancer Society · NOTel Aviv University · ILThe University of Melbourne · AUUniversity of Bonn · DEInternational Society for Gastrointestinal Hereditary Tumours · GBLeiden University Medical Center · NLLeipzig University · DETechnische Universität Dresden · DEUniversidad de Los Andes, Chile · CLUniversitätsklinikum Knappschaftskrankenhaus Bochum · DEUniversity of Oslo · NO

Funding

Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
NCI NIH HHS U01 CA167551
6 · The paper itself

Abstract

backgroundLynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown.

objectiveTo determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the

methodsCarriers of pathogenic variants of

resultsAmong 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately.

conclusionTruncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of

Indexed as

aberrant splicingcancer incidenceLynch syndromemissenseMLH1MSH2penetrancetruncating

Identifiers

PMID34203177
PMCPMC8269121
OpenAlexW3177433615

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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.