Evidence map›Paper›PMID 31337882›Full record

Observational studyGenetics in medicine : official journal of the American College of Medical Genetics2020

Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.

Mev Dominguez-Valentin, Julian R Sampson, Toni T Seppälä, Sanne W Ten Broeke, John-Paul Plazzer, Sigve Nakken, Christoph Engel, Stefan Aretz, Mark A Jenkins, Lone Sunde and 78 more

Erratum issued Registry-linked trialOpen access · hybridAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06582914 (Lynch Syndrome Integrative Epidemiology and Genetics), which is not on this map. Cited by 367 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
367citing papers in PubMed, 9 pooled it
40.3field-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.

NCT06582914 recruitingnot on this mapstarted 2024, after this paper: background citation

Lynch Syndrome Integrative Epidemiology and Genetics (LINEAGE)

Typeobservational_patient_registrySponsorUniversity of Colorado, DenverRan2024 to 2054Enrolled5,000ConditionsLynch Syndrome
3 · Its place in the literature

Who cites it

367 citing papers in PubMed, 9 syntheses or guidelines pooled it, 627 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Pooled it
  4. Genotype-phenotype correlations inOncology reviews · 2025
    Pooled it
  5. Guideline
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Trial
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Characterisation of a Portuguese origin founder missense variant in MSH6.European journal of human genetics : EJHG · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Article

307 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

88 authors at 20 institutions in 17 countries.

Mev Dominguez-Valentin *Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. mev.dominguez.valentin@rr-research.no.ORCID http://orcid.org/0000-0001-7856-0057
Julian R Sampson *Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK. sampson@cardiff.ac.uk.ORCID http://orcid.org/0000-0002-2902-2348
Toni T Seppälä *Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Helsinki, Finland. toni.seppala@fimnet.fi.ORCID http://orcid.org/0000-0002-4940-3498
Sanne W Ten BroekeDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
John-Paul PlazzerColorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
Sigve NakkenDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Christoph EngelInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Stefan AretzInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Mark A JenkinsCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
Lone SundeDepartment of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
Inge BernsteinDepartment of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
Gabriel CapellaHereditary Cancer Program, Institut Catal. d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Francesc BalaguerGastroenterology Department, Hospital Clinic 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, Barcelona, Spain.
Huw ThomasSt Mark's Hospital, Department of Surgery and Cancer, Imperial College London, London, UK.
D Gareth EvansManchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
John BurnInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Marc GreenblattUniversity of Vermont College of Medicine, Burlington, VT, USA.
Eivind HovigDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Wouter H de Vos Tot Nederveen CappelDepartment of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
Rolf H SijmonsDepartment of Genetics, University Medical Center Groningen, Groningen, The Netherlands.
Lucio BertarioUnit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori and Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy.
Maria Grazia TibilettiOspedale di Circolo ASST Settelaghi, Centro di Ricerca tumori eredo-familiari, Università dell'Insubria, Varese, Italy.
Giulia Martina CavestroGastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
Annika LindblomDepartment of Molecular Medicine and Surgery and Department of Clinical Genetics, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Adriana Della ValleHospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay.
Francisco Lopez-KöstnerLab. Oncología y Genética Molecular, Unidad de coloproctología, Clínica Las Condes, Santiago, Chile.
Nathan GluckDepartment of Gastroenterology, Tel Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Lior H KatzHigh Risk and GI Cancer prevention Clinic, Gastro-Oncology Unit, The Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel.
Karl HeinimannInstitute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Carlos A VaccaroHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Reinhard BüttnerInstitute of Pathology, University of Cologne, Cologne, Germany.
Heike GörgensDepartment of Surgical Research, Technische Universität Dresden, Dresden, Germany.
Elke Holinski-FederMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Monika MorakMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Stefanie HolzapfelInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Robert HüneburgDepartment of Internal Medicine, University Hospital Bonn, Bonn, Germany.
Magnus von Knebel DoeberitzDepartment of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Markus LoefflerInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Nils RahnerInstitute of Human Genetics, Medical School, Heinrich-Heine-University, Dusseldorf, Germany.
Hans K SchackertDepartment of Surgical Research, Technische Universität Dresden, Dresden, Germany.
Verena Steinke-LangeMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Wolff SchmiegelDepartment of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
Deepak VangalaDepartment of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
Kirsi PylvänäinenDepartment of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.
Laura Renkonen-SinisaloDepartment of Gastrointestinal Surgery, Helsinki University Central Hospital, Helsinki, Finland.
John L HopperCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
Aung Ko WinCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
Robert W HaileDepartment of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Palo Alto, CA, USA.
Noralane M LindorDepartment of Health Science Research, Mayo Clinic Arizona, Phoenix, AZ, USA.
Steven GallingerLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
Loïc Le MarchandUniversity of Hawaii Cancer Center, Honolulu, HI, USA.
Polly A NewcombPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Jane C FigueiredoCedars-Sinai Medical Center, Los Angeles, CA, USA.
Stephen N ThibodeauDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Karin WadtDepartment of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark.
Christina TherkildsenThe Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
Henrik OkkelsDepartment of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.
Zohreh KetabiDepartment of Obstetrics and Gynaecology, Copenhagen University Hospital, Rigshospitalet, Denmark.
Leticia MoreiraGastroenterology Department, Hospital Clinic 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, Barcelona, Spain.
Ariadna SánchezGastroenterology Department, Hospital Clinic 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, Barcelona, Spain.
Miquel Serra-BurrielUniversitat de Barcelona & Centre de Recerca en Economia i Salut (CRES-UPF), Barcelona, Spain.
Marta PinedaHereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Matilde NavarroHereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Ignacio BlancoHereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Kate GreenManchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Fiona LallooManchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Emma J CrosbieDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and St Mary's Hospital, Manchester, UK.
James HillDepartment of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
Oliver G DentonInstitute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
Ian M FraylingInstitute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
Einar Andreas RødlandDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Hans VasenDepartment of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
Miriam MintsDepartment of Women's and Children's health, Division of Obstetrics and Gyneacology, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
Florencia NeffaHospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay.
Patricia EsperonHospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay.
Karin AlvarezLab. Oncología y Genética Molecular, Unidad de coloproctología, Clínica Las Condes, Santiago, Chile.
Revital KarivDepartment of Gastroenterology, Tel Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Guy RosnerDepartment of Gastroenterology, Tel Aviv Sourasky Medical Centre and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Tamara Alejandra PineroHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
María Laura GonzalezHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Pablo KalfayanHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Douglas TjandraDepartment of Medicine, Melbourne University, Melbourne, Australia.
Ingrid M WinshipDepartment of Medicine, Melbourne University, Melbourne, Australia.
Finlay MacraeColorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
Gabriela MösleinSurgical Center for Hereditary Tumors, HELIOS University Clinic Wuppertal, University of Witten-Hardecke, Wuppertal, Germany.
Jukka-Pekka MecklinDepartments of Surgery, University of Jyväskylä and Central Finland Central Hospital, Jyväskylä, Finland.
Maartje NielsenDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Pål MøllerDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Oslo University Hospital · NOUniversity of Manchester · GBInstitut d'Investigació Biomédica de Bellvitge · ESThe University of Melbourne · AUCardiff University · GBHospital Central de las Fuerzas Armadas · UYHospital Clínic de Barcelona · ESLMU Klinikum · DETel Aviv University · ILThe Royal Melbourne Hospital · AUAalborg University Hospital · DKCentral Finland Health Care District · FIClínica Las Condes · CLConsejo Nacional de Investigaciones Científicas y Técnicas · ARCopenhagen University Hospital · DKHospital Italiano de Buenos Aires · ARKarolinska University Hospital · SELeiden University Medical Center · NLLeipzig University · DETechnische Universität Dresden · DE

Funding

USC Consortium:Colorectal Cancer Family RegistryU01CA074799 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAILE, ROBERT WILLIAM · 1997 to 2008
$20.4M
Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
SEATTLE FAMILIAL COLORECTAL CANCER REGISTRYU01CA074794 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NEWCOMB, POLLY A · 1997 to 2007
$14.1M
ONTARIO REGISTRY FOR STUDIES OF FAMILIAL COLON CANCERU01CA074783 · NCI · CANCER CARE ONTARIO · PI GALLINGER, STEVEN · 1997 to 2008
$12.5M
Colon Cancer Family Registry CohortUM1CA167551 · NCI · STANFORD UNIVERSITY · PI HAILE, ROBERT WILLIAM, JENKINS, MARK A · 2013 to 2017
$11.3M
Ethnic/Racial Minorities in the Colon CFRR01CA104132 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI LE MARCHAND, LOIC · 2004 to 2008
$9.5M
FAMILIAL COLORECTAL NEOPLASIA COLLABORATIVE GROUPU01CA074800 · NCI · MAYO CLINIC ROCHESTER · PI LINDOR, NORALANE MOREY · 1997 to 2007
$9.1M
The Colon Cancer Family Registry: USC ConsortiumU24CA074799 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HAILE, ROBERT WILLIAM · 2008 to 2011
$7.6M
The Colon Cancer Family Registry: SeattleU24CA074794 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NEWCOMB, POLLY A · 2008 to 2011
$7.0M
AUSTRALASIAN COLORECTAL CANCER FAMILY REGISTRYU01CA097735 · NCI · UNIVERSITY OF MELBOURNE · PI HOPPER, JOHN L · 2002 to 2007
$6.9M
The Colon Cancer Family Registry: AustralasiaU24CA097735 · NCI · UNIVERSITY OF MELBOURNE · PI HOPPER, JOHN L · 2008 to 2011
$6.2M
HAWAII FAMILY REGISTRY OF COLON CANCERU01CA074806 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI LE MARCHAND, LOIC · 1997 to 2008
$6.1M
Department of Health IS-BRC-1215–20007Department of Health NIHR-CS-012-009NCI NIH HHS R01 CA104132NCI NIH HHS U01 CA074783NCI NIH HHS U01 CA074794NCI NIH HHS U01 CA074799NCI NIH HHS U01 CA074800NCI NIH HHS U01 CA074806NCI NIH HHS U01 CA097735NCI NIH HHS U01 CA167551NCI NIH HHS U24 CA074783NCI NIH HHS U24 CA074794NCI NIH HHS U24 CA074799NCI NIH HHS U24 CA074800NCI NIH HHS U24 CA074806NCI NIH HHS U24 CA097735NCI NIH HHS UM1 CA167551
6 · The paper itself

Abstract

purposePathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer.

methodsWe conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years.

resultsThere were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer.

conclusionManagement guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.

Indexed as

MutationAdultAgedColorectal Neoplasms, Hereditary NonpolyposisDatabases, GeneticDNA-Binding ProteinsDNA Mismatch RepairFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedMismatch Repair Endonuclease PMS2MutL Protein Homolog 1MutS Homolog 2 ProteinPenetranceDNA-Binding ProteinsG-T mismatch-binding proteinMismatch Repair Endonuclease PMS2MLH1 protein, humanMSH2 protein, humanMutL Protein Homolog 1MutS Homolog 2 ProteinPMS2 protein, humanLynch syndromeMLH1MSH2MSH6PMS2

Identifiers

PMID31337882
PMCPMC7371626
OpenAlexW2951438828

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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.