1Research Group Inherited Cancer, Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway2Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Part of Oslo University Hospital, Oslo, Norway3Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland4The Danish Hereditary Non-polyposis Colorectal Cancer Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark5Department Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark6Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany7MGZ—Medizinisch Genetisches Zentrum, Munich, Germany8Unit of Hereditary Digestive Tract Tumors IRCCS, Istituto Nazionale Tumori, Milan, Italy9Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK10Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK11Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden12Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Victoria, Australia13Department of Medicine, Melbourne University, Melbourne, Australia14Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain15Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands16Institute of Medical Genetics, Cardiff University School of Medicine, Cardiff, UK17Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands18Institute of Genetic Medicine Newcastle University, Newcastle upon Tyne, UK19Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, Part of Oslo University Hospital, Oslo, Norway20Department of Informatics, University of Oslo, Oslo, Norway21Department of Mathematics and Statistics, Lancaster University, Lancaster, UK22Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands23Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK24Department of Clinical Genetics and Department of Human Genetics Leiden University Medical Centre, Leiden, The Netherlands25Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia26Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark27Department of Biomedicine, Aarhus University, Aarhus, Denmark28Division of Obstetrics and Gynecology, Department of Women's and Children's health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden29Department of Surgery, Helsinki University Hospital, Helsinki, Finland30Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland31Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland32Institute of Genomic Medicine, “A. Gemelli” Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy33University of Eastern Finland, Jyvaskyla, Finland34Surgical Center for Hereditary Tumors, HELIOS University Clinic Wuppertal, University Witten-Herdecke, Wuppertal, Germany
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ObjectiveToday most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers?DesignInformation was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants.Results1273 patients with LS from 10 countries were followed up for 7753 observation years. 318 patients (25.7%) developed 341 first subsequent cancers, including colorectal (n=147, 43%), upper GI, pancreas or bile duct (n=37, 11%) and urinary tract (n=32, 10%). The cumulative incidences for any subsequent cancer from age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year crude survival after CRC was 91% (95% CI 83% to 95%).ConclusionsRelative incidence of subsequent cancer compared with incidence of first cancer was slightly but insignificantly higher than cancer incidence in patients with LS without previous cancer (range 0.94–1.49). The favourable survival after subsequent cancers validated continued follow-up to prevent death from cancer. The interactive website http://lscarisk.org was expanded to calculate the risks by gender, genetic variant and age for subsequent cancer for any patient with LS with previous cancer.