Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium
Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention grou...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Hereditary Cancer in Clinical Practice |
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| Online Access: | https://doi.org/10.1186/s13053-022-00241-1 |
| _version_ | 1811253705333276672 |
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| author | Pål Møller Toni Seppälä James G. Dowty Saskia Haupt Mev Dominguez-Valentin Lone Sunde Inge Bernstein Christoph Engel Stefan Aretz Maartje Nielsen Gabriel Capella Dafydd Gareth Evans John Burn Elke Holinski-Feder Lucio Bertario Bernardo Bonanni Annika Lindblom Zohar Levi Finlay Macrae Ingrid Winship John-Paul Plazzer Rolf Sijmons Luigi Laghi Adriana Della Valle Karl Heinimann Elizabeth Half Francisco Lopez-Koestner Karin Alvarez-Valenzuela Rodney J. Scott Lior Katz Ido Laish Elez Vainer Carlos Alberto Vaccaro Dirce Maria Carraro Nathan Gluck Naim Abu-Freha Aine Stakelum Rory Kennelly Des Winter Benedito Mauro Rossi Marc Greenblatt Mabel Bohorquez Harsh Sheth Maria Grazia Tibiletti Leonardo S. Lino-Silva Karoline Horisberger Carmen Portenkirchner Ivana Nascimento Norma Teresa Rossi Leandro Apolinário da Silva Huw Thomas Attila Zaránd Jukka-Pekka Mecklin Kirsi Pylvänäinen Laura Renkonen-Sinisalo Anna Lepisto Päivi Peltomäki Christina Therkildsen Lars Joachim Lindberg Ole Thorlacius-Ussing Magnus von Knebel Doeberitz Markus Loeffler Nils Rahner Verena Steinke-Lange Wolff Schmiegel Deepak Vangala Claudia Perne Robert Hüneburg Aída Falcón de Vargas Andrew Latchford Anne-Marie Gerdes Ann-Sofie Backman Carmen Guillén-Ponce Carrie Snyder Charlotte K. Lautrup David Amor Edenir Palmero Elena Stoffel Floor Duijkers Michael J. Hall Heather Hampel Heinric Williams Henrik Okkels Jan Lubiński Jeanette Reece Joanne Ngeow Jose G. Guillem Julie Arnold Karin Wadt Kevin Monahan Leigha Senter Lene J. Rasmussen Liselotte P. van Hest Luigi Ricciardiello Maija R. J. Kohonen-Corish Marjolijn J. L. Ligtenberg Melissa Southey Melyssa Aronson Mohd N. Zahary N. Jewel Samadder Nicola Poplawski Nicoline Hoogerbrugge Patrick J. Morrison Paul James Grant Lee Rakefet Chen-Shtoyerman Ravindran Ankathil Rish Pai Robyn Ward Susan Parry Tadeusz Dębniak Thomas John Thomas van Overeem Hansen Trinidad Caldés Tatsuro Yamaguchi Verónica Barca-Tierno Pilar Garre Giulia Martina Cavestro Jürgen Weitz Silke Redler Reinhard Büttner Vincent Heuveline John L. Hopper Aung Ko Win Noralane Lindor Steven Gallinger Loïc Le Marchand Polly A. Newcomb Jane Figueiredo Daniel D. Buchanan Stephen N. Thibodeau Sanne W. ten Broeke Eivind Hovig Sigve Nakken Marta Pineda Nuria Dueñas Joan Brunet Kate Green Fiona Lalloo Katie Newton Emma J. Crosbie Miriam Mints Douglas Tjandra Florencia Neffa Patricia Esperon Revital Kariv Guy Rosner Walter Hernán Pavicic Pablo Kalfayan Giovana Tardin Torrezan Thiago Bassaneze Claudia Martin Gabriela Moslein Aysel Ahadova Matthias Kloor Julian R. Sampson Mark A. Jenkins The European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC) |
| author_facet | Pål Møller Toni Seppälä James G. Dowty Saskia Haupt Mev Dominguez-Valentin Lone Sunde Inge Bernstein Christoph Engel Stefan Aretz Maartje Nielsen Gabriel Capella Dafydd Gareth Evans John Burn Elke Holinski-Feder Lucio Bertario Bernardo Bonanni Annika Lindblom Zohar Levi Finlay Macrae Ingrid Winship John-Paul Plazzer Rolf Sijmons Luigi Laghi Adriana Della Valle Karl Heinimann Elizabeth Half Francisco Lopez-Koestner Karin Alvarez-Valenzuela Rodney J. Scott Lior Katz Ido Laish Elez Vainer Carlos Alberto Vaccaro Dirce Maria Carraro Nathan Gluck Naim Abu-Freha Aine Stakelum Rory Kennelly Des Winter Benedito Mauro Rossi Marc Greenblatt Mabel Bohorquez Harsh Sheth Maria Grazia Tibiletti Leonardo S. Lino-Silva Karoline Horisberger Carmen Portenkirchner Ivana Nascimento Norma Teresa Rossi Leandro Apolinário da Silva Huw Thomas Attila Zaránd Jukka-Pekka Mecklin Kirsi Pylvänäinen Laura Renkonen-Sinisalo Anna Lepisto Päivi Peltomäki Christina Therkildsen Lars Joachim Lindberg Ole Thorlacius-Ussing Magnus von Knebel Doeberitz Markus Loeffler Nils Rahner Verena Steinke-Lange Wolff Schmiegel Deepak Vangala Claudia Perne Robert Hüneburg Aída Falcón de Vargas Andrew Latchford Anne-Marie Gerdes Ann-Sofie Backman Carmen Guillén-Ponce Carrie Snyder Charlotte K. Lautrup David Amor Edenir Palmero Elena Stoffel Floor Duijkers Michael J. Hall Heather Hampel Heinric Williams Henrik Okkels Jan Lubiński Jeanette Reece Joanne Ngeow Jose G. Guillem Julie Arnold Karin Wadt Kevin Monahan Leigha Senter Lene J. Rasmussen Liselotte P. van Hest Luigi Ricciardiello Maija R. J. Kohonen-Corish Marjolijn J. L. Ligtenberg Melissa Southey Melyssa Aronson Mohd N. Zahary N. Jewel Samadder Nicola Poplawski Nicoline Hoogerbrugge Patrick J. Morrison Paul James Grant Lee Rakefet Chen-Shtoyerman Ravindran Ankathil Rish Pai Robyn Ward Susan Parry Tadeusz Dębniak Thomas John Thomas van Overeem Hansen Trinidad Caldés Tatsuro Yamaguchi Verónica Barca-Tierno Pilar Garre Giulia Martina Cavestro Jürgen Weitz Silke Redler Reinhard Büttner Vincent Heuveline John L. Hopper Aung Ko Win Noralane Lindor Steven Gallinger Loïc Le Marchand Polly A. Newcomb Jane Figueiredo Daniel D. Buchanan Stephen N. Thibodeau Sanne W. ten Broeke Eivind Hovig Sigve Nakken Marta Pineda Nuria Dueñas Joan Brunet Kate Green Fiona Lalloo Katie Newton Emma J. Crosbie Miriam Mints Douglas Tjandra Florencia Neffa Patricia Esperon Revital Kariv Guy Rosner Walter Hernán Pavicic Pablo Kalfayan Giovana Tardin Torrezan Thiago Bassaneze Claudia Martin Gabriela Moslein Aysel Ahadova Matthias Kloor Julian R. Sampson Mark A. Jenkins The European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC) |
| author_sort | Pål Møller |
| collection | DOAJ |
| description | Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so. |
| first_indexed | 2024-04-12T16:55:02Z |
| format | Article |
| id | doaj.art-b931c1477d4f40ef8fbc4e978abfdf69 |
| institution | Directory Open Access Journal |
| issn | 1897-4287 |
| language | English |
| last_indexed | 2024-04-12T16:55:02Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditary Cancer in Clinical Practice |
| spelling | doaj.art-b931c1477d4f40ef8fbc4e978abfdf692022-12-22T03:24:16ZengBMCHereditary Cancer in Clinical Practice1897-42872022-10-0120111110.1186/s13053-022-00241-1Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortiumPål Møller0Toni Seppälä1James G. Dowty2Saskia Haupt3Mev Dominguez-Valentin4Lone Sunde5Inge Bernstein6Christoph Engel7Stefan Aretz8Maartje Nielsen9Gabriel Capella10Dafydd Gareth Evans11John Burn12Elke Holinski-Feder13Lucio Bertario14Bernardo Bonanni15Annika Lindblom16Zohar Levi17Finlay Macrae18Ingrid Winship19John-Paul Plazzer20Rolf Sijmons21Luigi Laghi22Adriana Della Valle23Karl Heinimann24Elizabeth Half25Francisco Lopez-Koestner26Karin Alvarez-Valenzuela27Rodney J. Scott28Lior Katz29Ido Laish30Elez Vainer31Carlos Alberto Vaccaro32Dirce Maria Carraro33Nathan Gluck34Naim Abu-Freha35Aine Stakelum36Rory Kennelly37Des Winter38Benedito Mauro Rossi39Marc Greenblatt40Mabel Bohorquez41Harsh Sheth42Maria Grazia Tibiletti43Leonardo S. Lino-Silva44Karoline Horisberger45Carmen Portenkirchner46Ivana Nascimento47Norma Teresa Rossi48Leandro Apolinário da Silva49Huw Thomas50Attila Zaránd51Jukka-Pekka Mecklin52Kirsi Pylvänäinen53Laura Renkonen-Sinisalo54Anna Lepisto55Päivi Peltomäki56Christina Therkildsen57Lars Joachim Lindberg58Ole Thorlacius-Ussing59Magnus von Knebel Doeberitz60Markus Loeffler61Nils Rahner62Verena Steinke-Lange63Wolff Schmiegel64Deepak Vangala65Claudia Perne66Robert Hüneburg67Aída Falcón de Vargas68Andrew Latchford69Anne-Marie Gerdes70Ann-Sofie Backman71Carmen Guillén-Ponce72Carrie Snyder73Charlotte K. Lautrup74David Amor75Edenir Palmero76Elena Stoffel77Floor Duijkers78Michael J. Hall79Heather Hampel80Heinric Williams81Henrik Okkels82Jan Lubiński83Jeanette Reece84Joanne Ngeow85Jose G. Guillem86Julie Arnold87Karin Wadt88Kevin Monahan89Leigha Senter90Lene J. Rasmussen91Liselotte P. van Hest92Luigi Ricciardiello93Maija R. J. Kohonen-Corish94Marjolijn J. L. Ligtenberg95Melissa Southey96Melyssa Aronson97Mohd N. Zahary98N. Jewel Samadder99Nicola Poplawski100Nicoline Hoogerbrugge101Patrick J. Morrison102Paul James103Grant Lee104Rakefet Chen-Shtoyerman105Ravindran Ankathil106Rish Pai107Robyn Ward108Susan Parry109Tadeusz Dębniak110Thomas John111Thomas van Overeem Hansen112Trinidad Caldés113Tatsuro Yamaguchi114Verónica Barca-Tierno115Pilar Garre116Giulia Martina Cavestro117Jürgen Weitz118Silke Redler119Reinhard Büttner120Vincent Heuveline121John L. Hopper122Aung Ko Win123Noralane Lindor124Steven Gallinger125Loïc Le Marchand126Polly A. Newcomb127Jane Figueiredo128Daniel D. Buchanan129Stephen N. Thibodeau130Sanne W. ten Broeke131Eivind Hovig132Sigve Nakken133Marta Pineda134Nuria Dueñas135Joan Brunet136Kate Green137Fiona Lalloo138Katie Newton139Emma J. Crosbie140Miriam Mints141Douglas Tjandra142Florencia Neffa143Patricia Esperon144Revital Kariv145Guy Rosner146Walter Hernán Pavicic147Pablo Kalfayan148Giovana Tardin Torrezan149Thiago Bassaneze150Claudia Martin151Gabriela Moslein152Aysel Ahadova153Matthias Kloor154Julian R. Sampson155Mark A. Jenkins156The European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC)Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium HospitalDepartment of Gastrointestinal Surgery, Helsinki University Central Hospital, University of HelsinkiCentre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbourneEngineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg UniversityDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium HospitalDepartment of Clinical Genetics, Aalborg University HospitalDepartment of Surgical Gastroenterology, Aalborg University Hospital, Aalborg UniversityInstitute for Medical Informatics, Statistics and Epidemiology, University of LeipzigInstitute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University of BonnDepartment of Clinical Genetics, Leids Universitair Medisch CentrumHereditary Cancer Program, Institut Català d’Oncologia-IDIBELL, L; Hospitalet de LlobregatDivision of Evolution and Genomic Sciences, Manchester Centre for Genomic Medicine, University of Manchester, Manchester University NHS Foundation TrustTranslational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle UniversityCampus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität MünchenDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCSDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCSDepartment of Molecular Medicine and Surgery, Karolinska InstitutetDepartment Rabin Medical Center, Service High Risk GI Cancer GastroenterologyColorectal Medicine and Genetics, The Royal Melbourne HospitalColorectal Medicine and Genetics, The Royal Melbourne HospitalThe Royal Melbourne HospitalDepartment of Genetics, University of Groningen, University Medical Center GroningenDepartment of Medicine and Surgery, Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, University of ParmaHospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU)Medical Genetics, Institute for Medical Genetics and Pathology, University Hospital BaselGastrointestinal Cancer Prevention Unit, Gastroenterology Department, Rambam Health Care CampusPrograma Cáncer Heredo Familiar Clínica Universidad de los AndePrograma Cáncer Heredo Familiar Clínica Universidad de los AndeUniversity of Newcastle and the Hunter Medical Research InstituteDepartment of Gastroenterology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of JerusalemThe Department of Gastroenterology, High Risk and GI Cancer Prevention Clinic, Gastro-Oncology Unit, Sheba Medical CenterDepartment of Gastroenterology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of JerusalemHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos AiresGenomic and Molecular Biology Group, A.C.Camargo Cancer CenterDepartment of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv UniversityThe Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Ben-Gurion University of the NegevSt Vincent’s University HospitalSt Vincent’s University HospitalSt Vincent’s University HospitalHospital Sirio LibanesUniversity of Vermont, Larner College of MedicineUniversity of TolimaFoundation for Research in Genetics and Endocrinology, FRIGE HouseOspedale di Circolo ASST Settelaghi, Centro di Ricerca Tumori Eredo-Familiari, Università dell’InsubriaInstituto Nacional de CancerologiaDepartment of Abdominal and Transplantation Surgery, Universitätsspital ZürichDepartment of Abdominal and Transplantation Surgery, Universitätsspital ZürichLaboratório de Imonologia, ICS/UFBA, Núcleo de Oncologia da Bahia/OncoclinicasHospital Privado Universitario de CórdobaHospital Universitario Oswaldo Cruz, Universidade de Pernambuco, Hospital de Câncer de Pernambuco, IPON - Instituto de Pesquisas Oncológicas do NordesteDepartment of Surgery and Cancer, St Mark’s Hospital, Imperial College LondonDepartment of Transplantation and Surgery, Semmelweis University BudapestFaculty of Sport and Health Sciences, University of JyväskyläDepartment of Education and Science, Central Finland Health Care DistrictDepartment of Gastrointestinal Surgery, Helsinki University Central Hospital, University of HelsinkiDepartment of Gastrointestinal Surgery, Helsinki University Central Hospital, University of HelsinkiDepartment of Medical and Clinical Genetics, University of HelsinkiThe Danish HNPCC Register, Gastro Unit, Copenhagen University Hospital – Amager and HvidovreThe Danish HNPCC Register, Gastro Unit, Copenhagen University Hospital – Amager and HvidovreDepartment of Surgical Gastroenterology, Aalborg University Hospital, Aalborg UniversityDepartment of Applied Tumour Biology, Institute of Pathology, University Hospital HeidelbergInstitute for Medical Informatics, Statistics and Epidemiology, University of LeipzigInstitute of Human Genetics, University Clinic Düsseldorf, Heinrich-Heine-UniversityCampus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität MünchenDepartment of Medicine, Knappschaftskrankenhaus, Ruhr-University BochumDepartment of Medicine, Knappschaftskrankenhaus, Ruhr-University BochumInstitute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University of BonnDepartment of Internal Medicine, University Hospital BonnGenetics Unit, Hospital Vargas de CaracasSt Mark’s HospitalDepartment of Clinical Genetics, Rigshospitalet, Copenhagen University HospitalDepartment of Medicine Solna, Unit of Internal medicine, Karolinska InstitutetMedical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCISHereditary Cancer Center, Department of Preventive Medicine, Creighton UniversityDepartment of Clinical Genetics, Aalborg University HospitalMurdoch Children’s Research Institute and University of Melbourne Department of Paediatrics, Royal Children’s HospitalDepartment of Genetics, Brazilian National Cancer InstituteDepartment of Internal Medicine, University of MichiganDepartment of Clinical Genetics, Amsterdam University Medical Centers, University of AmsterdamDepartment of Clinical Genetics, Fox Chase Cancer CenterDivision of Human Genetics, The Ohio State University Comprehensive Cancer CenterDepartment of Urology, Geisinger Medical CenterDepartment of Molecular Diagnostics, Aalborg UniversityDepartment of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in SzczecinCentre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbourneLee Kong Chian School of Medicine, Nanyang Technological University Singapore and Cancer Genetics Service National Cancer Centre SingaporeGastrointestinal Surgery, University of North CarolinaNew Zealand Familial Gastrointestinal Cancer ServiceDepartment of Clinical Genetics, Rigshospitalet, Copenhagen University HospitalSt Mark’s Hospital & Imperial CollegeOhio State University Comprehensive Cancer CenterDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of CopenhagenDepartment of Clinical Genetics, Amsterdam UMC, Vrije Universiteit AmsterdamIRCCS AOU di Bologna, and Department of Medical and Surgical Sciences - University of BolognaWoolcock Institute of Medical Research, GlebeDepartment of Human Genetics and Department of Pathology, Radboud University Medical CenterMonash Health Translation Precinct, Monash UniversityZane Cohen Centre, Sinai Health SystemFaculty of Health Sciences, University Sultan Zainal AbidinDivision of Gastroenterology and Hepatology, Mayo ClinicAdelaide Medical School, University of AdelaideDepartment of Human Genetics, Radboud University Medical CenterRegional Medical Genetics Centre, Belfast HSC Trust, City Hospital Campus, Queen’s University BelfastPeter MacCallum Department of Oncology, The University of MelbourneGenomics Platform Group, Centre for Cancer Research, University of MelbourneThe Biology Department, Ariel University, Ariel and the Oncogenetic Clinic, The Clinical Genetics Institute, Kaplan Medical CenterHuman Genome Centre, School of Medical Sciences, Universiti Sains MalaysiaDepartment of Laboratory Medicine and Pathology, Mayo Clinic ArizonaFaculty of Medicine and Health, University of SydneyNew Zealand Familial Gastrointestinal Cancer ServiceDepartment of Genetics and Pathology, Pomeranian Medical University in SzczecinDepartment of Medical Oncology, Peter MacCallum Cancer CentreDepartment of Clinical Genetics, Rigshospitalet, Copenhagen University HospitalMolecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSCDepartment of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome HospitalDepartment of Genetics, Hospital Universitario Ramón y Cajal, IRYCISMolecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSCGastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific InstituteTechnische Universität DresdenInstitute of Human Genetics, University Clinic Düsseldorf, Heinrich-Heine-UniversityDepartment of Pathology, University Hospital of CologneEngineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg UniversityCentre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbourneCentre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbourneDepartment of Health Science Research, Mayo Clinic ArizonaLunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of TorontoUniversity of Hawaii Cancer CenterPublic Health Sciences Division, Fred Hutchinson Cancer Research CenterPublic Health Sciences Division, Fred Hutchinson Cancer Research CenterColorectal Oncogenomics Group, Department of Clinical Pathology, The University of MelbourneDepartment of Laboratory Medicine and Pathology, Mayo ClinicLeids Universitair Medisch CentrumDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium HospitalDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium HospitalHereditary Cancer Program, Institut Català d’Oncologia-IDIBELL, L; Hospitalet de LlobregatHereditary Cancer Program, Institut Català d’Oncologia-IDIBELL, L; Hospitalet de LlobregatHereditary Cancer Program, Institut Català d’Oncologia-IDIBELL, L; Hospitalet de LlobregatDivision of Evolution and Genomic Sciences, Manchester Centre for Genomic Medicine, University of Manchester, Manchester University NHS Foundation TrustDivision of Evolution and Genomic Sciences, Manchester Centre for Genomic Medicine, University of Manchester, Manchester University NHS Foundation TrustDepartment of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of ManchesterGynaecological Oncology Research Group, Manchester University NHS Foundation TrustDivision of Obstetrics and Gyneacology, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University HospitalColorectal Medicine and Genetics, The Royal Melbourne HospitalHospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU)Hospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU)Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv UniversityDepartment of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv UniversityHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos AiresHereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos AiresGenomic and Molecular Biology Group, A.C.Camargo Cancer CenterHospital Sirio LibanesHospital Universitario Oswaldo Cruz, Universidade de Pernambuco, Hospital de Câncer de Pernambuco, IPON - Instituto de Pesquisas Oncológicas do NordesteSurgical Center for Hereditary Tumors, Ev. Bethesda Khs Duisburg, University Witten-HerdeckeDepartment of Applied Tumour Biology, Institute of Pathology, University Hospital HeidelbergDepartment of Applied Tumour Biology, Institute of Pathology, University Hospital HeidelbergDivision of Cancer and Genetics, Institute of Medical Genetics, Cardiff University School of MedicineCentre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of MelbourneAbstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.https://doi.org/10.1186/s13053-022-00241-1Lynch SyndromeEpidemiologyPreventionPenetranceColorectal cancerSegregation analysis |
| spellingShingle | Pål Møller Toni Seppälä James G. Dowty Saskia Haupt Mev Dominguez-Valentin Lone Sunde Inge Bernstein Christoph Engel Stefan Aretz Maartje Nielsen Gabriel Capella Dafydd Gareth Evans John Burn Elke Holinski-Feder Lucio Bertario Bernardo Bonanni Annika Lindblom Zohar Levi Finlay Macrae Ingrid Winship John-Paul Plazzer Rolf Sijmons Luigi Laghi Adriana Della Valle Karl Heinimann Elizabeth Half Francisco Lopez-Koestner Karin Alvarez-Valenzuela Rodney J. Scott Lior Katz Ido Laish Elez Vainer Carlos Alberto Vaccaro Dirce Maria Carraro Nathan Gluck Naim Abu-Freha Aine Stakelum Rory Kennelly Des Winter Benedito Mauro Rossi Marc Greenblatt Mabel Bohorquez Harsh Sheth Maria Grazia Tibiletti Leonardo S. Lino-Silva Karoline Horisberger Carmen Portenkirchner Ivana Nascimento Norma Teresa Rossi Leandro Apolinário da Silva Huw Thomas Attila Zaránd Jukka-Pekka Mecklin Kirsi Pylvänäinen Laura Renkonen-Sinisalo Anna Lepisto Päivi Peltomäki Christina Therkildsen Lars Joachim Lindberg Ole Thorlacius-Ussing Magnus von Knebel Doeberitz Markus Loeffler Nils Rahner Verena Steinke-Lange Wolff Schmiegel Deepak Vangala Claudia Perne Robert Hüneburg Aída Falcón de Vargas Andrew Latchford Anne-Marie Gerdes Ann-Sofie Backman Carmen Guillén-Ponce Carrie Snyder Charlotte K. Lautrup David Amor Edenir Palmero Elena Stoffel Floor Duijkers Michael J. Hall Heather Hampel Heinric Williams Henrik Okkels Jan Lubiński Jeanette Reece Joanne Ngeow Jose G. Guillem Julie Arnold Karin Wadt Kevin Monahan Leigha Senter Lene J. Rasmussen Liselotte P. van Hest Luigi Ricciardiello Maija R. J. Kohonen-Corish Marjolijn J. L. Ligtenberg Melissa Southey Melyssa Aronson Mohd N. Zahary N. Jewel Samadder Nicola Poplawski Nicoline Hoogerbrugge Patrick J. Morrison Paul James Grant Lee Rakefet Chen-Shtoyerman Ravindran Ankathil Rish Pai Robyn Ward Susan Parry Tadeusz Dębniak Thomas John Thomas van Overeem Hansen Trinidad Caldés Tatsuro Yamaguchi Verónica Barca-Tierno Pilar Garre Giulia Martina Cavestro Jürgen Weitz Silke Redler Reinhard Büttner Vincent Heuveline John L. Hopper Aung Ko Win Noralane Lindor Steven Gallinger Loïc Le Marchand Polly A. Newcomb Jane Figueiredo Daniel D. Buchanan Stephen N. Thibodeau Sanne W. ten Broeke Eivind Hovig Sigve Nakken Marta Pineda Nuria Dueñas Joan Brunet Kate Green Fiona Lalloo Katie Newton Emma J. Crosbie Miriam Mints Douglas Tjandra Florencia Neffa Patricia Esperon Revital Kariv Guy Rosner Walter Hernán Pavicic Pablo Kalfayan Giovana Tardin Torrezan Thiago Bassaneze Claudia Martin Gabriela Moslein Aysel Ahadova Matthias Kloor Julian R. Sampson Mark A. Jenkins The European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC) Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium Hereditary Cancer in Clinical Practice Lynch Syndrome Epidemiology Prevention Penetrance Colorectal cancer Segregation analysis |
| title | Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium |
| title_full | Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium |
| title_fullStr | Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium |
| title_full_unstemmed | Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium |
| title_short | Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium |
| title_sort | colorectal cancer incidences in lynch syndrome a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium |
| topic | Lynch Syndrome Epidemiology Prevention Penetrance Colorectal cancer Segregation analysis |
| url | https://doi.org/10.1186/s13053-022-00241-1 |
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colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT elezvainer colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT carlosalbertovaccaro colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT dircemariacarraro colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT nathangluck colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT naimabufreha colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT ainestakelum 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colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT mariagraziatibiletti colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT leonardoslinosilva colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT karolinehorisberger colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT carmenportenkirchner colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT ivananascimento colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT normateresarossi 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colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT revitalkariv colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT guyrosner colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT walterhernanpavicic colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT pablokalfayan colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT giovanatardintorrezan colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT thiagobassaneze colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT claudiamartin colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT gabrielamoslein colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT ayselahadova colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT matthiaskloor colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT julianrsampson colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT markajenkins colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium AT theeuropeanhereditarytumourgroupehtgandtheinternationalmismatchrepairconsortiumimrc colorectalcancerincidencesinlynchsyndromeacomparisonofresultsfromtheprospectivelynchsyndromedatabaseandtheinternationalmismatchrepairconsortium |