Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Pål Møller¹, Toni Seppälä^{2

3

4}, James G Dowty⁵, Saskia Haupt^{6

7}, Mev Dominguez-Valentin⁸, Lone Sunde^{9

10}, Inge Bernstein^{11

12}, Christoph Engel¹³, Stefan Aretz¹⁴, Maartje Nielsen¹⁵, Gabriel Capella¹⁶, Dafydd Gareth Evans¹⁷, John Burn¹⁸, Elke Holinski-Feder^{19

20}, Lucio Bertario²¹, Bernardo Bonanni²¹, Annika Lindblom²², Zohar Levi²³, Finlay Macrae^{24

25}, Ingrid Winship^{24

25}, John-Paul Plazzer²⁶, Rolf Sijmons²⁷, Luigi Laghi²⁸, Adriana Della Valle²⁹, Karl Heinimann³⁰, Elizabeth Half³¹, Francisco Lopez-Koestner³², Karin Alvarez-Valenzuela³², Rodney J Scott³³, Lior Katz³⁴, Ido Laish³⁵, Elez Vainer³⁴, Carlos Alberto Vaccaro³⁶, Dirce Maria Carraro³⁷, Nathan Gluck³⁸, Naim Abu-Freha³⁹, Aine Stakelum⁴⁰, Rory Kennelly⁴⁰, Des Winter⁴⁰, Benedito Mauro Rossi⁴¹, Marc Greenblatt⁴², Mabel Bohorquez⁴³, Harsh Sheth⁴⁴, Maria Grazia Tibiletti⁴⁵, Leonardo S Lino-Silva⁴⁶, Karoline Horisberger⁴⁷, Carmen Portenkirchner⁴⁷, Ivana Nascimento⁴⁸, Norma Teresa Rossi⁴⁹, Leandro Apolinário da Silva⁵⁰, Huw Thomas⁵¹, Attila Zaránd⁵², Jukka-Pekka Mecklin^{53

54}, Kirsi Pylvänäinen⁵⁵, Laura Renkonen-Sinisalo^{2

3}, Anna Lepisto^{2

3}, Päivi Peltomäki⁵⁶, Christina Therkildsen⁵⁷, Lars Joachim Lindberg⁵⁷, Ole Thorlacius-Ussing^{11

12}, Magnus von Knebel Doeberitz^{58

59}, Markus Loeffler⁶⁰, Nils Rahner⁶¹, Verena Steinke-Lange^{19

20}, Wolff Schmiegel⁶², Deepak Vangala⁶², Claudia Perne¹⁴, Robert Hüneburg⁶³, Aída Falcón de Vargas^{64

65}, Andrew Latchford⁶⁶, Anne-Marie Gerdes⁶⁷, Ann-Sofie Backman⁶⁸, Carmen Guillén-Ponce⁶⁹, Carrie Snyder⁷⁰, Charlotte K Lautrup⁹, David Amor⁷¹, Edenir Palmero^{72

73}, Elena Stoffel⁷⁴, Floor Duijkers⁷⁵, Michael J Hall⁷⁶, Heather Hampel⁷⁷, Heinric Williams⁷⁸, Henrik Okkels⁷⁹, Jan Lubiński⁸⁰, Jeanette Reece⁵, Joanne Ngeow⁸¹, Jose G Guillem⁸², Julie Arnold⁸³, Karin Wadt⁶⁷, Kevin Monahan⁸⁴, Leigha Senter⁸⁵, Lene J Rasmussen⁸⁶, Liselotte P van Hest⁸⁷, Luigi Ricciardiello⁸⁸, Maija R J Kohonen-Corish⁸⁹, Marjolijn J L Ligtenberg⁹⁰, Melissa Southey⁹¹, Melyssa Aronson⁹², Mohd N Zahary⁹³, N Jewel Samadder⁹⁴, Nicola Poplawski^{95

96}, Nicoline Hoogerbrugge⁹⁷, Patrick J Morrison⁹⁸, Paul James⁹⁹, Grant Lee¹⁰⁰, Rakefet Chen-Shtoyerman¹⁰¹, Ravindran Ankathil¹⁰², Rish Pai¹⁰³, Robyn Ward¹⁰⁴, Susan Parry⁸³, Tadeusz Dębniak¹⁰⁵, Thomas John¹⁰⁶, Thomas van Overeem Hansen⁶⁷, Trinidad Caldés¹⁰⁷, Tatsuro Yamaguchi¹⁰⁸, Verónica Barca-Tierno¹⁰⁹, Pilar Garre¹⁰⁷, Giulia Martina Cavestro¹¹⁰, Jürgen Weitz¹¹¹, Silke Redler⁶¹, Reinhard Büttner¹¹², Vincent Heuveline⁶, John L Hopper⁵, Aung Ko Win⁵, Noralane Lindor¹¹³, Steven Gallinger¹¹⁴, Loïc Le Marchand¹¹⁵, Polly A Newcomb¹¹⁶, Jane Figueiredo¹¹⁶, Daniel D Buchanan^{117

118

119}, Stephen N Thibodeau¹²⁰, Sanne W Ten Broeke¹²¹, Eivind Hovig^{8

122}, Sigve Nakken^{8

123}, Marta Pineda¹⁶, Nuria Dueñas¹⁶, Joan Brunet¹⁶, Kate Green¹⁷, Fiona Lalloo¹⁷, Katie Newton¹²⁴, Emma J Crosbie^{125

126}, Miriam Mints¹²⁷, Douglas Tjandra^{24

25}, Florencia Neffa²⁹, Patricia Esperon²⁹, Revital Kariv³⁸, Guy Rosner³⁸, Walter Hernán Pavicic^{36

128}, Pablo Kalfayan³⁶, Giovana Tardin Torrezan³⁷, Thiago Bassaneze⁴¹, Claudia Martin⁵⁰, Gabriela Moslein¹²⁹, Aysel Ahadova⁵⁸, Matthias Kloor⁵⁸, Julian R Sampson¹³⁰, Mark A Jenkins⁵; European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC)

Affiliations

¹ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379, Oslo, Norway. moller.pal@gmail.com.
² Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
³ Applied Tumour Genomics Research Program, University of Helsinki, Helsinki, Finland.
⁴ Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
⁵ Centre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
⁶ Engineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany.
⁷ Data Mining and Uncertainty Quantification (DMQ), Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany.
⁸ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379, Oslo, Norway.
⁹ Department of Clinical Genetics, Aalborg University Hospital, 9000, Aalborg, Denmark.
¹⁰ Department of Biomedicine, Aarhus University, DK-8000, Aarhus, Denmark.
¹¹ Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg University, 9100, Aalborg, Denmark.
¹² Institute of Clinical Medicine, Aalborg University Hospital, Aalborg University, 9100, Aalborg, Denmark.
¹³ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107, Leipzig, Germany.
¹⁴ Institute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University of Bonn, 53127, Bonn, Germany.
¹⁵ Department of Clinical Genetics, Leids Universitair Medisch Centrum, 2300RC, Leiden, The Netherlands.
¹⁶ Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L; Hospitalet de Llobregat, 08908, Barcelona, Spain.
¹⁷ Division of Evolution and Genomic Sciences, Manchester Centre for Genomic Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, M13 9WL, UK.
¹⁸ Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
¹⁹ Campus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336, Munich, Germany.
²⁰ MGZ - Center of Medical Genetics, 80335, Munich, Germany.
²¹ Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, 20141, Milan, Italy.
²² Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76, Stockholm, Sweden.
²³ Department Rabin Medical Center, Service High Risk GI Cancer Gastroenterology, Petach Tikva, Israel.
²⁴ Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
²⁵ Department of Medicine, Melbourne University, Melbourne, Australia.
²⁶ The Royal Melbourne Hospital, Melbourne, Australia.
²⁷ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²⁸ Department of Medicine and Surgery, Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, University of Parma, Parma, Italy.
²⁹ Hospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay.
³⁰ Medical Genetics, Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
³¹ Gastrointestinal Cancer Prevention Unit, Gastroenterology Department, Rambam Health Care Campus, Haifa, Israel.
³² Programa Cáncer Heredo Familiar Clínica Universidad de los Ande, Santiago, Chile.
³³ University of Newcastle and the Hunter Medical Research Institute, Callaghan, Australia.
³⁴ Department of Gastroenterology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
³⁵ The Department of Gastroenterology, High Risk and GI Cancer Prevention Clinic, Gastro-Oncology Unit, Sheba Medical Center, Ramat Gan, Israel.
³⁶ Hereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
³⁷ Genomic and Molecular Biology Group, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
³⁸ Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
³⁹ The Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel.
⁴⁰ St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
⁴¹ Hospital Sirio Libanes, Sao Paulo, Brazil.
⁴² University of Vermont, Larner College of Medicine, Burlington, VT, 05405, USA.
⁴³ University of Tolima, Tolima, Colombia.
⁴⁴ Foundation for Research in Genetics and Endocrinology, FRIGE House, Jodhpur Village Road, Satellite Ahmedabad, Ahmedabad, 380015, India.
⁴⁵ Ospedale di Circolo ASST Settelaghi, Centro di Ricerca Tumori Eredo-Familiari, Università dell'Insubria, Varese, Italy.
⁴⁶ Instituto Nacional de Cancerologia, Mexico, DF, Mexico.
⁴⁷ Department of Abdominal and Transplantation Surgery, Universitätsspital Zürich, Rämistrasse 100, CH-8091, Zürich, Switzerland.
⁴⁸ Laboratório de Imonologia, ICS/UFBA, Núcleo de Oncologia da Bahia/Oncoclinicas, Salvador, Brazil.
⁴⁹ Hospital Privado Universitario de Córdoba, Cordoba, Argentina.
⁵⁰ Hospital Universitario Oswaldo Cruz, Universidade de Pernambuco, Hospital de Câncer de Pernambuco, IPON - Instituto de Pesquisas Oncológicas do Nordeste, Salvador, Brazil.
⁵¹ Department of Surgery and Cancer, St Mark's Hospital, Imperial College London, London, UK.
⁵² Department of Transplantation and Surgery, Semmelweis University Budapest, Budapest, Hungary.
⁵³ Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
⁵⁴ Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland.
⁵⁵ Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.
⁵⁶ Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
⁵⁷ The Danish HNPCC Register, Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.
⁵⁸ Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁵⁹ Clinical Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁰ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁶¹ Institute of Human Genetics, University Clinic Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
⁶² Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
⁶³ Department of Internal Medicine, University Hospital Bonn, Bonn, Germany.
⁶⁴ Genetics Unit, Hospital Vargas de Caracas, Caracas, Venezuela.
⁶⁵ Escuela de Medicina Jose Maria Vargas, Universidad, Central de Venezuela, UCV, Caracas, Venezuela.
⁶⁶ St Mark's Hospital, London, UK.
⁶⁷ Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, DK-2100, Copenhagen, Denmark.
⁶⁸ Department of Medicine Solna, Unit of Internal medicine, Karolinska Institutet, Stockholm, Sweden.
⁶⁹ Medical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
⁷⁰ Hereditary Cancer Center, Department of Preventive Medicine, Creighton University, Omaha, NE, 68178, USA.
⁷¹ Murdoch Children's Research Institute and University of Melbourne Department of Paediatrics, Royal Children's Hospital, Parkville, VIC, 3052, Australia.
⁷² Department of Genetics, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
⁷³ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
⁷⁴ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁷⁵ Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
⁷⁶ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁷⁷ Division of Human Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA.
⁷⁸ Department of Urology, Geisinger Medical Center, Danville, PA, 17822, USA.
⁷⁹ Department of Molecular Diagnostics, Aalborg University, Aalborg, Denmark.
⁸⁰ Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland.
⁸¹ Lee Kong Chian School of Medicine, Nanyang Technological University Singapore and Cancer Genetics Service National Cancer Centre Singapore, Singapore, Singapore.
⁸² Gastrointestinal Surgery, University of North Carolina, Chapel Hill, NC, USA.
⁸³ New Zealand Familial Gastrointestinal Cancer Service, Auckland, New Zealand.
⁸⁴ St Mark's Hospital & Imperial College, London, UK.
⁸⁵ Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA.
⁸⁶ Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
⁸⁷ Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
⁸⁸ IRCCS AOU di Bologna, and Department of Medical and Surgical Sciences - University of Bologna, Bologna, Italy.
⁸⁹ Woolcock Institute of Medical Research, Glebe, Sydney, NSW, 2037, Australia.
⁹⁰ Department of Human Genetics and Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁹¹ Monash Health Translation Precinct, Monash University, Clayton South, VIC, 3169, Australia.
⁹² Zane Cohen Centre, Sinai Health System, Toronto, Ontario, Canada.
⁹³ Faculty of Health Sciences, University Sultan Zainal Abidin, Kuala Terengganu, Terengganu, Malaysia.
⁹⁴ Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, 85054, USA.
⁹⁵ Adelaide Medical School, University of Adelaide, Adelaide, SA, 5000, Australia.
⁹⁶ Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia.
⁹⁷ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
⁹⁸ Regional Medical Genetics Centre, Belfast HSC Trust, City Hospital Campus, Queen's University Belfast, Belfast, Northern Ireland, UK.
⁹⁹ Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.
¹⁰⁰ Genomics Platform Group, Centre for Cancer Research, University of Melbourne, Parkville, VIC, Australia.
¹⁰¹ The Biology Department, Ariel University, Ariel and the Oncogenetic Clinic, The Clinical Genetics Institute, Kaplan Medical Center, Rehovot, Israel.
¹⁰² Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
¹⁰³ Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, 85259, USA.
¹⁰⁴ Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2006, Australia.
¹⁰⁵ Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.
¹⁰⁶ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹⁰⁷ Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
¹⁰⁸ Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
¹⁰⁹ Department of Genetics, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
¹¹⁰ Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
¹¹¹ Technische Universität Dresden, Dresden, Germany.
¹¹² Department of Pathology, University Hospital of Cologne, Cologne, Germany.
¹¹³ Department of Health Science Research, Mayo Clinic Arizona, Phoenix, USA.
¹¹⁴ Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
¹¹⁵ University of Hawaii Cancer Center, Honolulu, USA.
¹¹⁶ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.
¹¹⁷ Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
¹¹⁸ University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
¹¹⁹ Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Victoria, Australia.
¹²⁰ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
¹²¹ Leids Universitair Medisch Centrum, Leiden, Netherlands.
¹²² Department of Informatics, Centre for Bioinformatics, University of Oslo, Oslo, Norway.
¹²³ Centre for Cancer Cell Reprogramming (CanCell), Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹²⁴ Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
¹²⁵ Gynaecological Oncology Research Group, Manchester University NHS Foundation Trust, Manchester, UK.
¹²⁶ Division of Cancer Sciences, University of Manchester, Manchester, UK.
¹²⁷ Division of Obstetrics and Gyneacology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
¹²⁸ Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB), Hospital Italiano de Buenos Aires-IUHI-CONICET, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
¹²⁹ Surgical Center for Hereditary Tumors, Ev. Bethesda Khs Duisburg, University Witten-Herdecke, Herdecke, Germany.
¹³⁰ Division of Cancer and Genetics, Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.

PMID: 36182917
PMCID: PMC9526951
DOI: 10.1186/s13053-022-00241-1

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Pål Møller et al. Hered Cancer Clin Pract. 2022.

. 2022 Oct 1;20(1):36.

doi: 10.1186/s13053-022-00241-1.

Authors

Affiliations

¹ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379, Oslo, Norway. moller.pal@gmail.com.
² Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
³ Applied Tumour Genomics Research Program, University of Helsinki, Helsinki, Finland.
⁴ Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Tampere, Finland.
⁵ Centre of Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
⁶ Engineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany.
⁷ Data Mining and Uncertainty Quantification (DMQ), Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany.
⁸ Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379, Oslo, Norway.
⁹ Department of Clinical Genetics, Aalborg University Hospital, 9000, Aalborg, Denmark.
¹⁰ Department of Biomedicine, Aarhus University, DK-8000, Aarhus, Denmark.
¹¹ Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg University, 9100, Aalborg, Denmark.
¹² Institute of Clinical Medicine, Aalborg University Hospital, Aalborg University, 9100, Aalborg, Denmark.
¹³ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107, Leipzig, Germany.
¹⁴ Institute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University of Bonn, 53127, Bonn, Germany.
¹⁵ Department of Clinical Genetics, Leids Universitair Medisch Centrum, 2300RC, Leiden, The Netherlands.
¹⁶ Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L; Hospitalet de Llobregat, 08908, Barcelona, Spain.
¹⁷ Division of Evolution and Genomic Sciences, Manchester Centre for Genomic Medicine, University of Manchester, Manchester University NHS Foundation Trust, Manchester, M13 9WL, UK.
¹⁸ Translational & Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
¹⁹ Campus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336, Munich, Germany.
²⁰ MGZ - Center of Medical Genetics, 80335, Munich, Germany.
²¹ Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, 20141, Milan, Italy.
²² Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76, Stockholm, Sweden.
²³ Department Rabin Medical Center, Service High Risk GI Cancer Gastroenterology, Petach Tikva, Israel.
²⁴ Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
²⁵ Department of Medicine, Melbourne University, Melbourne, Australia.
²⁶ The Royal Melbourne Hospital, Melbourne, Australia.
²⁷ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²⁸ Department of Medicine and Surgery, Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, University of Parma, Parma, Italy.
²⁹ Hospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay.
³⁰ Medical Genetics, Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
³¹ Gastrointestinal Cancer Prevention Unit, Gastroenterology Department, Rambam Health Care Campus, Haifa, Israel.
³² Programa Cáncer Heredo Familiar Clínica Universidad de los Ande, Santiago, Chile.
³³ University of Newcastle and the Hunter Medical Research Institute, Callaghan, Australia.
³⁴ Department of Gastroenterology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
³⁵ The Department of Gastroenterology, High Risk and GI Cancer Prevention Clinic, Gastro-Oncology Unit, Sheba Medical Center, Ramat Gan, Israel.
³⁶ Hereditary Cancer Program (PROCANHE), Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
³⁷ Genomic and Molecular Biology Group, A.C.Camargo Cancer Center, Sao Paulo, Brazil.
³⁸ Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
³⁹ The Institute of Gastroenterology and Hepatology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel.
⁴⁰ St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
⁴¹ Hospital Sirio Libanes, Sao Paulo, Brazil.
⁴² University of Vermont, Larner College of Medicine, Burlington, VT, 05405, USA.
⁴³ University of Tolima, Tolima, Colombia.
⁴⁴ Foundation for Research in Genetics and Endocrinology, FRIGE House, Jodhpur Village Road, Satellite Ahmedabad, Ahmedabad, 380015, India.
⁴⁵ Ospedale di Circolo ASST Settelaghi, Centro di Ricerca Tumori Eredo-Familiari, Università dell'Insubria, Varese, Italy.
⁴⁶ Instituto Nacional de Cancerologia, Mexico, DF, Mexico.
⁴⁷ Department of Abdominal and Transplantation Surgery, Universitätsspital Zürich, Rämistrasse 100, CH-8091, Zürich, Switzerland.
⁴⁸ Laboratório de Imonologia, ICS/UFBA, Núcleo de Oncologia da Bahia/Oncoclinicas, Salvador, Brazil.
⁴⁹ Hospital Privado Universitario de Córdoba, Cordoba, Argentina.
⁵⁰ Hospital Universitario Oswaldo Cruz, Universidade de Pernambuco, Hospital de Câncer de Pernambuco, IPON - Instituto de Pesquisas Oncológicas do Nordeste, Salvador, Brazil.
⁵¹ Department of Surgery and Cancer, St Mark's Hospital, Imperial College London, London, UK.
⁵² Department of Transplantation and Surgery, Semmelweis University Budapest, Budapest, Hungary.
⁵³ Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
⁵⁴ Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland.
⁵⁵ Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.
⁵⁶ Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
⁵⁷ The Danish HNPCC Register, Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark.
⁵⁸ Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁵⁹ Clinical Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁰ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁶¹ Institute of Human Genetics, University Clinic Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
⁶² Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
⁶³ Department of Internal Medicine, University Hospital Bonn, Bonn, Germany.
⁶⁴ Genetics Unit, Hospital Vargas de Caracas, Caracas, Venezuela.
⁶⁵ Escuela de Medicina Jose Maria Vargas, Universidad, Central de Venezuela, UCV, Caracas, Venezuela.
⁶⁶ St Mark's Hospital, London, UK.
⁶⁷ Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, DK-2100, Copenhagen, Denmark.
⁶⁸ Department of Medicine Solna, Unit of Internal medicine, Karolinska Institutet, Stockholm, Sweden.
⁶⁹ Medical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
⁷⁰ Hereditary Cancer Center, Department of Preventive Medicine, Creighton University, Omaha, NE, 68178, USA.
⁷¹ Murdoch Children's Research Institute and University of Melbourne Department of Paediatrics, Royal Children's Hospital, Parkville, VIC, 3052, Australia.
⁷² Department of Genetics, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.
⁷³ Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
⁷⁴ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁷⁵ Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
⁷⁶ Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁷⁷ Division of Human Genetics, The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA.
⁷⁸ Department of Urology, Geisinger Medical Center, Danville, PA, 17822, USA.
⁷⁹ Department of Molecular Diagnostics, Aalborg University, Aalborg, Denmark.
⁸⁰ Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University in Szczecin, Szczecin, Poland.
⁸¹ Lee Kong Chian School of Medicine, Nanyang Technological University Singapore and Cancer Genetics Service National Cancer Centre Singapore, Singapore, Singapore.
⁸² Gastrointestinal Surgery, University of North Carolina, Chapel Hill, NC, USA.
⁸³ New Zealand Familial Gastrointestinal Cancer Service, Auckland, New Zealand.
⁸⁴ St Mark's Hospital & Imperial College, London, UK.
⁸⁵ Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA.
⁸⁶ Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
⁸⁷ Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
⁸⁸ IRCCS AOU di Bologna, and Department of Medical and Surgical Sciences - University of Bologna, Bologna, Italy.
⁸⁹ Woolcock Institute of Medical Research, Glebe, Sydney, NSW, 2037, Australia.
⁹⁰ Department of Human Genetics and Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁹¹ Monash Health Translation Precinct, Monash University, Clayton South, VIC, 3169, Australia.
⁹² Zane Cohen Centre, Sinai Health System, Toronto, Ontario, Canada.
⁹³ Faculty of Health Sciences, University Sultan Zainal Abidin, Kuala Terengganu, Terengganu, Malaysia.
⁹⁴ Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, 85054, USA.
⁹⁵ Adelaide Medical School, University of Adelaide, Adelaide, SA, 5000, Australia.
⁹⁶ Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, SA, 5000, Australia.
⁹⁷ Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
⁹⁸ Regional Medical Genetics Centre, Belfast HSC Trust, City Hospital Campus, Queen's University Belfast, Belfast, Northern Ireland, UK.
⁹⁹ Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, 3010, Australia.
¹⁰⁰ Genomics Platform Group, Centre for Cancer Research, University of Melbourne, Parkville, VIC, Australia.
¹⁰¹ The Biology Department, Ariel University, Ariel and the Oncogenetic Clinic, The Clinical Genetics Institute, Kaplan Medical Center, Rehovot, Israel.
¹⁰² Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
¹⁰³ Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, 85259, USA.
¹⁰⁴ Faculty of Medicine and Health, University of Sydney, Sydney, NSW, 2006, Australia.
¹⁰⁵ Department of Genetics and Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland.
¹⁰⁶ Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
¹⁰⁷ Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
¹⁰⁸ Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
¹⁰⁹ Department of Genetics, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
¹¹⁰ Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
¹¹¹ Technische Universität Dresden, Dresden, Germany.
¹¹² Department of Pathology, University Hospital of Cologne, Cologne, Germany.
¹¹³ Department of Health Science Research, Mayo Clinic Arizona, Phoenix, USA.
¹¹⁴ Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
¹¹⁵ University of Hawaii Cancer Center, Honolulu, USA.
¹¹⁶ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.
¹¹⁷ Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
¹¹⁸ University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
¹¹⁹ Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Victoria, Australia.
¹²⁰ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
¹²¹ Leids Universitair Medisch Centrum, Leiden, Netherlands.
¹²² Department of Informatics, Centre for Bioinformatics, University of Oslo, Oslo, Norway.
¹²³ Centre for Cancer Cell Reprogramming (CanCell), Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹²⁴ Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
¹²⁵ Gynaecological Oncology Research Group, Manchester University NHS Foundation Trust, Manchester, UK.
¹²⁶ Division of Cancer Sciences, University of Manchester, Manchester, UK.
¹²⁷ Division of Obstetrics and Gyneacology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
¹²⁸ Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB), Hospital Italiano de Buenos Aires-IUHI-CONICET, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
¹²⁹ Surgical Center for Hereditary Tumors, Ev. Bethesda Khs Duisburg, University Witten-Herdecke, Herdecke, Germany.
¹³⁰ Division of Cancer and Genetics, Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.

PMID: 36182917
PMCID: PMC9526951
DOI: 10.1186/s13053-022-00241-1

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.

Keywords: Colonoscopy; Colorectal cancer; Epidemiology; Incidence; Lynch Syndrome; Over-diagnosis; Penetrance; Prevention; Prospective; Segregation analysis.

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Conflict of interest statement

L Senter-Jamieson have received speaking/consultant fees from AstraZeneca in the past year. Carmen Guillén-Ponce: registrations for congresses and continuing education courses by Merck, Sanofi and Astra Zeneca. Toni T. Seppälä reports CEO and co-owner of Healthfund Finland and an interview honoraria from Boehringer Ingelheim Finland. All other authors declare no conflict of interest.

Figures

**Fig. 1**
Cumulative incidences of CRC by genetic variant and gender in PLSD (the prospective series with colonoscopy) and IMRC (the retrospective series) in European *path_MLH1, path_MSH2* and *path_MSH6* carriers. Broken lines indicate 95% confidence intervals

See this image and copyright information in PMC

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Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

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Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

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