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

Lynch syndrome MLH1 MSH2 aberrant splicing cancer incidence missense penetrance truncating

Journal

Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588

Informations de publication

Date de publication:
28 Jun 2021
Historique:
received: 24 05 2021
revised: 15 06 2021
accepted: 16 06 2021
entrez: 2 7 2021
pubmed: 3 7 2021
medline: 3 7 2021
Statut: epublish

Résumé

Lynch 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. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the Carriers of pathogenic variants of Among 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. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of

Sections du résumé

BACKGROUND BACKGROUND
Lynch 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.
OBJECTIVE OBJECTIVE
To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the
METHODS METHODS
Carriers of pathogenic variants of
RESULTS RESULTS
Among 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.
CONCLUSION CONCLUSIONS
Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of

Identifiants

DOI: 10.3390/jcm10132856 PMID: 34203177 PMC: PMC8269121
pubmed: 34203177
pii: jcm10132856
doi: 10.3390/jcm10132856
pmc: PMC8269121
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : NCI NIH HHS
ID : U01 CA167551
Pays : United States

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Auteurs

Mev Dominguez-Valentin (M)

Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.
European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
ORCID: 0000-0001-7856-0057

John-Paul Plazzer (JP)

The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Department of Medicine, Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.
ORCID: 0000-0001-5114-4301

Julian R Sampson (JR)

European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

Christoph Engel (C)

European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany.
ORCID: 0000-0002-7247-282X

Stefan Aretz (S)

Institute 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 Jenkins (MA)

Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC 3010, Australia.

Lone Sunde (L)

Department of Clinical Genetics, Aalborg University Hospital, 9000 Aalborg, Denmark.
Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.

Inge Bernstein (I)

Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg University, 9100 Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University Hospital, Aalborg University, 9100 Aalborg, Denmark.

Gabriel Capella (G)

European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L, Hospitalet de Llobregat, 08908 Barcelona, Spain.
ORCID: 0000-0002-4669-7320

Francesc Balaguer (F)

Gastroenterology 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 Macrae (F)

The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Department of Medicine, Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.

Ingrid M Winship (IM)

Department of Genomic Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3052, Australia.
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3052, Australia.

Huw Thomas (H)

Department of Surgery and Cancer, St Mark's Hospital, Imperial College London, London HA1 3UJ, UK.

Dafydd Gareth Evans (DG)

Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
ORCID: 0000-0002-8482-5784

John Burn (J)

European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
ORCID: 0000-0002-9823-2322

Marc Greenblatt (M)

Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.

Wouter H de Vos Tot Nederveen Cappel (WH)

Department of Gastroenterology and Hepatology, Isala Clinics, 8015 Zwolle, The Netherlands.
ORCID: 0000-0002-3956-1206

Rolf H Sijmons (RH)

European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Department of Genetics, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands.

Maartje Nielsen (M)

Department of Clinical Genetics, Leids Universitair Medisch Centrum, 2300RC Leiden, The Netherlands.
ORCID: 0000-0002-5351-1870

Lucio Bertario (L)

Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, IRCCS, 20141 Milan, Italy.

Bernardo Bonanni (B)

Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, 20141 Milan, Italy.
ORCID: 0000-0003-3589-2128

Maria Grazia Tibiletti (MG)

Ospedale di Circolo ASST Settelaghi, Centro di Ricerca Tumori Eredo-Familiari, Università dell'Insubria, 21100 Varese, Italy.

Giulia Martina Cavestro (GM)

Gastroenterology and Gastrointestinal Endoscopy Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy.

Annika Lindblom (A)

Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden.

Adriana Della Valle (AD)

Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Hospital Fuerzas Armadas, Montevideo 11600, Uruguay.

Francisco Lopez-Kostner (F)

Programa Cáncer Heredo Familiar, Clínica Universidad de los Andes, Santiago 7550000, Chile.

Karin Alvarez (K)

Programa Cáncer Heredo Familiar, Clínica Universidad de los Andes, Santiago 7550000, Chile.

Nathan Gluck (N)

Department of Gastroenterology, Sackler Faculty of Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv 64259, Israel.
ORCID: 0000-0001-5503-488X

Lior Katz (L)

The Department of Gastroenterology, Gastro-Oncology Unit, High Risk and GI Cancer Prevention Clinic, Sheba Medical Center, Sheba 91120, Israel.

Karl Heinimann (K)

Medical Genetics, Institute for Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, Switzerland.

Carlos A Vaccaro (CA)

Hereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.
Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB), CONICET IU, Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.
ORCID: 0000-0002-1299-5864

Sigve Nakken (S)

Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.
Centre for Cancer Cell Reprogramming (CanCell), Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 4950 Oslo, Norway.
ORCID: 0000-0001-8468-2050

Eivind Hovig (E)

Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.
Department of Informatics, Centre for Bioinformatics, University of Oslo, 0316 Oslo, Norway.
ORCID: 0000-0002-9103-1077

Kate Green (K)

Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.

Fiona Lalloo (F)

Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.

James Hill (J)

Department of Surgery, Central Manchester University Hospitals NHS, Foundation Trust, University of Manchester, London M13 9WL, UK.

Hans F A Vasen (HFA)

Department of Gastroenterology and Hepatology, Leiden University Medical Centre, 2333 Leiden, The Netherlands.

Claudia Perne (C)

Institute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.

Reinhard Büttner (R)

Institute of Pathology, University of Cologne, 50937 Cologne, Germany.

Heike Görgens (H)

Department of Surgery, Technische Universität Dresden, 01062 Dresden, Germany.

Elke Holinski-Feder (E)

The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Campus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.
Center of Medical Genetics, 80335 Munich, Germany.

Monika Morak (M)

Campus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.
Center of Medical Genetics, 80335 Munich, Germany.

Stefanie Holzapfel (S)

Institute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.

Robert Hüneburg (R)

Department of Internal Medicine, University Hospital Bonn, 53127 Bonn, Germany.
ORCID: 0000-0001-9957-8299

Magnus von Knebel Doeberitz (M)

Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Markus Loeffler (M)

Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany.

Nils Rahner (N)

Medical School, Institute of Human Genetics, Heinrich-Heine-University, 40225 Dusseldorf, Germany.

Jürgen Weitz (J)

Department of Surgery, Technische Universität Dresden, 01062 Dresden, Germany.

Verena Steinke-Lange (V)

Campus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.
Center of Medical Genetics, 80335 Munich, Germany.
ORCID: 0000-0001-8491-3234

Wolff Schmiegel (W)

Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, D-44789 Bochum, Germany.

Deepak Vangala (D)

Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, D-44789 Bochum, Germany.
ORCID: 0000-0002-4175-5683

Emma J Crosbie (EJ)

Gynaecological 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 Pineda (M)

Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L, Hospitalet de Llobregat, 08908 Barcelona, Spain.
ORCID: 0000-0002-5403-5845

Matilde Navarro (M)

Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L, Hospitalet de Llobregat, 08908 Barcelona, Spain.

Joan Brunet (J)

Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L, Hospitalet de Llobregat, 08908 Barcelona, Spain.
ORCID: 0000-0003-1945-3512

Leticia Moreira (L)

Gastroenterology 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 Sánchez (A)

Gastroenterology 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-Burriel (M)

Centre de Recerca en Economia i Salut (CRES-UPF), Universitat de Barcelona, 08002 Barcelona, Spain.

Miriam Mints (M)

Division of Obstetrics and Gyneacology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Solna, 171 77 Stockholm, Sweden.

Revital Kariv (R)

Department of Gastroenterology, Sackler Faculty of Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv 64259, Israel.

Guy Rosner (G)

Department of Gastroenterology, Sackler Faculty of Medicine, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel-Aviv 64259, Israel.

Tamara Alejandra Piñero (TA)

Hereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.
Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB), CONICET IU, Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.

Walter Hernán Pavicic (WH)

Hereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.
Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB), CONICET IU, Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.
ORCID: 0000-0001-7840-4943

Pablo Kalfayan (P)

Hereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Buenos Aires C1199ABB, Argentina.

Sanne W Ten Broeke (SWT)

Department of Clinical Genetics, Leids Universitair Medisch Centrum, 2300RC Leiden, The Netherlands.
ORCID: 0000-0001-6280-0087

Jukka-Pekka Mecklin (JP)

European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Departments of Surgery, Central Finland Hospital Nova, University of Jyväskylä, 40620 Jyväskylä, Finland.

Kirsi Pylvänäinen (K)

Department 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-Sinisalo (L)

Applied Tumour Genomics Research Program, University of Helsinki, 00014 Helsinki, Finland.
Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, 00280 Helsinki, Finland.

Anna Lepistö (A)

Applied Tumour Genomics Research Program, University of Helsinki, 00014 Helsinki, Finland.
Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, 00280 Helsinki, Finland.

Päivi Peltomäki (P)

Department of Medical and Clinical Genetics, University of Helsinki, 00014 Helsinki, Finland.

John L Hopper (JL)

Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, VIC 3010, Australia.

Aung Ko Win (AK)

Melbourne 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 Buchanan (DD)

Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3010, Australia.
Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.
Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, VIC 3010, Australia.
ORCID: 0000-0003-2225-6675

Noralane M Lindor (NM)

Department of Health Science Research, Mayo Clinic Arizona, Phoenix, AZ 85054, USA.

Steven Gallinger (S)

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON M5G 1X5, Canada.

Loïc Le Marchand (LL)

Cancer Center, University of Hawaii, Honolulu, HI 96813, USA.
ORCID: 0000-0001-5013-980X

Polly A Newcomb (PA)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.

Jane C Figueiredo (JC)

Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Stephen N Thibodeau (SN)

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.

Christina Therkildsen (C)

The Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, 2560 Hvidovre, Denmark.

Thomas V O Hansen (TVO)

Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.

Lars Lindberg (L)

Gastro Unit, Copenhagen University Hospital, 2560 Hvidovre, Denmark.

Einar Andreas Rødland (EA)

Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.
ORCID: 0000-0002-9780-8385

Florencia Neffa (F)

Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Hospital Fuerzas Armadas, Montevideo 11600, Uruguay.

Patricia Esperon (P)

Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Hospital Fuerzas Armadas, Montevideo 11600, Uruguay.
ORCID: 0000-0002-3080-5702

Douglas Tjandra (D)

Department of Medicine, Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, VIC 3050, Australia.
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC 3052, Australia.
ORCID: 0000-0002-2236-5225

Gabriela Möslein (G)

European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Surgical Center for Hereditary Tumors, Ev. Bethesda Khs Duisburg, University Witten-Herdecke, 58448 Herdecke, Germany.

Toni T Seppälä (TT)

European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, 00280 Helsinki, Finland.
Department of Surgical Oncology, Johns Hopkins Hospital, Baltimore, MA 21287, USA.
ORCID: 0000-0002-4940-3498

Pål Møller (P)

Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379 Oslo, Norway.
European Hereditary Tumour Group (EHTG), c/o Lindsays, Caledonian Exchange 19A Canning Street, Edinburgh EH3 8HE, UK.
The International Society for Gastrointestinal Hereditary Tumours (InSiGHT), The Polyposis Registry, St Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK.

Classifications MeSH