Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database.

Autor:	Dominguez-Valentin M; Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379, Oslo, Norway., Haupt S; Engineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany.; Data Mining and Uncertainty Quantification (DMQ), Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany., Seppälä TT; Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, Finland.; Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.; Applied Tumor Genomics, Research Program Unit, University of Helsinki, Helsinki, Finland., Sampson JR; Division of Cancer and Genetics, Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK., Sunde L; Department of Clinical Genetics, Aalborg University Hospital, 9000, Aalborg, Denmark.; Department of Biomedicine, Aarhus University, DK-8000, Aarhus, Denmark., 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., Jenkins MA; Melbourne School of Population and Global Health, Centre for Epidemiology and Biostatistics, The University of Melbourne, Parkville, 3010, Victoria, Australia., Engel C; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107, Leipzig, Germany., Aretz S; Institute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany., Nielsen M; Department of Clinical Genetics, Leids Universitair Medisch Centrum, 2300RC, Leiden, the Netherlands., Capella G; Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L; Hospitalet de Llobregat, 08908, Barcelona, Spain., 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, Barcelona, Spain., Evans DG; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, M13 9WL, UK., Burn J; Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE1 7RU, UK., Holinski-Feder E; Campus Innenstadt, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336, Munich, Germany.; Center of Medical Genetics, 80335, Munich, Germany., Bertario L; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, Fondazione IRCCS Instituto Nazionale dei Tumori, IRCCS, 20141, Milan, Italy., Bonanni B; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, 20141, Milan, Italy., Lindblom A; Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76, Stockholm, Sweden., Levi Z; Service High Risk GI Cancer Gastroenterology, Department Rabin Medical Center, Israel., Macrae F; Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.; Department of Medicine, Melbourne University, Melbourne, Australia., Winship I; Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.; Department of Medicine, Melbourne University, Melbourne, Australia.; Department of Medicine, University of Melbourne, Melbourne, Australia., Plazzer JP; Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.; Department of Medicine, Melbourne University, Melbourne, Australia., Sijmons R; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Laghi L; Department of Medicine and Surgery, Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, University of Parma, Parma, Italy., Della Valle A; Hospital Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Montevideo, Uruguay., Heinimann K; Medical Genetics, Institute for Medical Genetics and Pathology, University Hospital Basel, Switzerland., Dębniak T; Department of Genetics and Pathology, International Hereditary Cancer Center, ul. Unii Lubelskiej 1, 71-252, Szczecin, Poland., Fruscio R; Department of Medicine and Surgery, University of Milan Bicocca, A.O. San Gerardo, Clinic of Obstetrics and Gynecology, Via Pergolesi 33, Monza (MB), Italy., Lopez-Koestner F; Clínica Universidad de los Andes, Chile.; Programa Cáncer Heredo Familiar, Santiago, Chile., Alvarez-Valenzuela K; Clínica Universidad de los Andes, Chile.; Programa Cáncer Heredo Familiar, Santiago, Chile., Katz LH; Department of Gastroenterology, Hadassah, Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Israel., Laish I; Department of Gastroenterology, Hadassah, Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Israel., Vainer E; Hadassah Medical Center, Israel., Vaccaro C; Hereditary Cancer Program (PROCANHE) Hospital Italiano de Buenos Aires, Argentina., Carraro DM; Clinical and Functional Genomics Group, A.C.Camargo Cancer Center, Sao Paulo, Brazil., Monahan K; Lynch Syndrome & Family Cancer Clinic, St Mark's Hospital, Harrow, HA1 3UJ, London, UK., Half E; Gastrointestinal Cancer Prevention Unit, Gastroenterology Department, Rambam Health Care Campus, Haifa, Israel., Stakelum A; St Vincent's University Hospital, Ireland., Winter D; St Vincent's University Hospital, Ireland., Kennelly R; St Vincent's University Hospital, Ireland., Gluck N; Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Israel., Sheth H; Foundation for Research in Genetics and Endocrinology, Institute of Human Genetics, FRIGE House, Ahmedabad, 380015, India., Abu-Freha N; Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Southern Israel, Israel., Greenblatt M; University of Vermont, Larner College of Medicine, Burlington, VT, 05405, USA., Rossi BM; Hospital Sirio Libanes, Sao Paulo, Brazil., Bohorquez M; University of Tolima, Tolima, Colombia., Cavestro GM; Gastroenterology and Gastrointestinal Endoscopy Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132, Milan, Italy., Lino-Silva LS; Surgical Pathology, Instituto Nacional de Cancerologia, Mexico City, Mexico., Horisberger K; Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Switzerland.; Depart-ment of Surgery, Universitätsmedizin Mainz, Germany., Tibiletti MG; Ospedale di Circolo ASST Settelaghi, Centro di Ricerca tumori eredo-familiari, Università dell'Insubria, Varese, Italy., Nascimento ID; Universidade Federal de Bahia, Bahia, Brazil., Thomas H; St Mark's Hospital, Department of Surgery and Cancer, Imperial College London, London, UK., Rossi NT; Fundación para el Progreso de la Medicina' y 'Sanatorio Allende', Córdoba, Argentina., Apolinário da Silva L; Hospital Universitário Oswaldo Cruz, Universidade de Pernambuco, Recife, Brazil.; SEQUIPE, Recife, Brazil., Zaránd A; 1st Department of Surgery, Semmelweis University, Hungary., Ruiz-Bañobre J; Department of Medical Oncology, University Clinical Hospital of Santiago de Compostela (SERGAS); Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela (IDIS); Genomes and Disease, Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela (USC), 15706, Santiago de Compostela, Spain.; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029, Madrid, Spain., Heuveline V; Engineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany.; Data Mining and Uncertainty Quantification (DMQ), Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany., Mecklin JP; Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.; Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland., Pylvänäinen K; Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland., Renkonen-Sinisalo L; Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.; Applied Tumor Genomics, Research Program Unit, University of Helsinki, Helsinki, Finland., Lepistö A; Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.; Applied Tumor Genomics, Research Program Unit, University of Helsinki, Helsinki, Finland., Peltomäki P; Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland., Therkildsen C; The Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark., Madsen MG; Department of Urology, Aarhus University Hospital, Denmark., Burgdorf SK; Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Denmark., Hopper JL; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia., Win AK; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia., Haile RW; Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, USA., Lindor N; Department of Health Science Research, Mayo Clinic Arizona, USA., Gallinger S; Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Canada., Le Marchand L; University of Hawaii Cancer Center, USA., Newcomb PA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA., Figueiredo J; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA., Buchanan DD; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.; Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Victoria, Australia., Thibodeau SN; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA., von Knebel Doeberitz M; Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.; Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Loeffler M; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107, Leipzig, Germany., Rahner N; Institute of Human Genetics, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Germany., Schröck E; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.; German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.; Institute for Clinical Genetics, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.; Hereditary Cancer Syndrome Center Dresden, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany., Steinke-Lange V; Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.; MGZ - Medical Genetics Center, Munich, Germany., Schmiegel W; Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany., Vangala D; Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany., Perne C; Institute of Human Genetics, National Center for Hereditary Tumor Syndromes, Medical Faculty, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany., Hüneburg R; Department of Internal Medicine, University Hospital Bonn, Bonn, Germany., Redler S; Institute of Human Genetics, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Germany., Büttner R; Institute of Pathology, Faculty of Medicine and University Hospital Cologne, Cologne, Germany., Weitz J; Technische Universität Dresden, Dresden, Germany., Pineda M; Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L; Hospitalet de Llobregat, 08908, Barcelona, Spain., Duenas N; Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L; Hospitalet de Llobregat, 08908, Barcelona, Spain., Vidal JB; Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L; Hospitalet de Llobregat, 08908, Barcelona, Spain., 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, Barcelona, Spain., 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, Barcelona, Spain., Hovig E; Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379, Oslo, Norway.; Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway., Nakken S; Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379, Oslo, Norway.; Centre for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway.; Centre for Cancer Cell Reprogramming (CanCell), Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Green K; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, M13 9WL, UK., Lalloo F; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, M13 9WL, UK., Hill J; Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, London, UK., Crosbie E; Gynaecological Oncology Research Group, Manchester University NHS Foundation Trust, Manchester, UK.; Division of Cancer Sciences, University of Manchester, Manchester, UK., Mints M; Division of Obstetrics and Gyneacology, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden., Goldberg Y; Head Adult Genetic Service, Raphael Recanati Genetic Institute, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel., Tjandra D; Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.; Department of Medicine, Melbourne University, Melbourne, Australia., Ten Broeke SW; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Kariv R; St Vincent's University Hospital, Ireland., Rosner G; St Vincent's University Hospital, Ireland., Advani SH; Sushrut Hospital and Research Centre, Mumbai, India., Thomas L; Sushrut Hospital and Research Centre, Mumbai, India., Shah P; Zydus Cancer Centre, Ahmedabad, India., Shah M; Zydus Cancer Centre, Ahmedabad, India., Neffa F; Department of Medicine and Surgery, Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, University of Parma, Parma, Italy., Esperon P; Department of Medicine and Surgery, Laboratory of Molecular Gastroenterology, IRCCS Humanitas Research Hospital, University of Parma, Parma, Italy., Pavicic W; Instituto de Medicina Traslacional e Ingenieria Biomedica (IMTIB), CONICET IU, Hospital Italiano de Buenos Aires, Buenos Aires, 94, Argentina., Torrezan GT; Hereditary Cancer Program (PROCANHE) Hospital Italiano de Buenos Aires, Argentina., Bassaneze T; University of Vermont, Larner College of Medicine, Burlington, VT, 05405, USA., Martin CA; Hospital Privado Universiatrio de Córdoba, Cordoba, Argentina., Moslein G; Surgical Center for Hereditary Tumors, Ev. Bethesda Khs Duisburg, University Witten-Herdecke, Herdecke, Germany., Moller P; Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0379, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2023 Mar 20; Vol. 58, pp. 101909. Date of Electronic Publication: 2023 Mar 20 (Print Publication: 2023).
DOI:	10.1016/j.eclinm.2023.101909
Abstrakt:	Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants ( path_MMR ) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017. Competing Interests: R.B. has received honoraria for lectures and advisory boards from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Illumina, Lilly, Merck-Serono, MSD, Novartis, Qiagen, Pfizer, Roche, and Targos MP Inc. R.B. is a Co-Founder and Scientific Advisor for Targos Mol. Pathology Inc. Kassel/Germany. T.T.S. is the CEO and co-owner of Healthfund Finland Oy and reports consultation fees from Boehringer Ingelheim Finland and Amgen. FB is supported by JANSSEN PHARMACEUTICALS (clinical trial for Familial Adenomatous polyposis). RH is supported by the 10.13039/501100002424Fujifilm Germany and Janssen-Pharmaceuticals. LK is consultant of Sandoz, Novartis and Abbott. GM reports consultancy fees from Johnson & Johnson. (© 2023 The Author(s).)
Databáze:	MEDLINE
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