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Original article
Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database
  1. Pål Møller1,2,34,
  2. Toni Seppälä3,
  3. Inge Bernstein4,5,
  4. Elke Holinski-Feder6,7,
  5. Paola Sala8,
  6. D Gareth Evans9,10,
  7. Annika Lindblom11,
  8. Finlay Macrae12,13,
  9. Ignacio Blanco14,
  10. Rolf Sijmons15,
  11. Jacqueline Jeffries16,
  12. Hans Vasen17,
  13. John Burn18,
  14. Sigve Nakken2,
  15. Eivind Hovig2,19,20,
  16. Einar Andreas Rødland2,
  17. Kukatharmini Tharmaratnam21,
  18. Wouter H de Vos tot Nederveen Cappel22,
  19. James Hill23,
  20. Juul Wijnen24,
  21. Mark Jenkins25,
  22. Kate Green9,
  23. Fiona Lalloo9,
  24. Lone Sunde4,26,27,
  25. Miriam Mints28,
  26. Lucio Bertario8,
  27. Marta Pineda14,
  28. Matilde Navarro14,
  29. Monika Morak6,7,
  30. Laura Renkonen-Sinisalo29,30,
  31. Ian M Frayling16,
  32. John-Paul Plazzer12,
  33. Kirsi Pylvanainen31,
  34. Maurizio Genuardi32,
  35. Jukka-Pekka Mecklin31,33,
  36. Gabriela Möslein34,
  37. Julian R Sampson16,
  38. Gabriel Capella14,
  39. in collaboration with The Mallorca Group (http://mallorca-group.org)
  1. 1Research Group Inherited Cancer, Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  2. 2Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Part of Oslo University Hospital, Oslo, Norway
  3. 3Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland
  4. 4The Danish Hereditary Non-polyposis Colorectal Cancer Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark
  5. 5Department Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
  6. 6Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany
  7. 7MGZ—Medizinisch Genetisches Zentrum, Munich, Germany
  8. 8Unit of Hereditary Digestive Tract Tumors IRCCS, Istituto Nazionale Tumori, Milan, Italy
  9. 9Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  10. 10Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK
  11. 11Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  12. 12Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
  13. 13Department of Medicine, Melbourne University, Melbourne, Australia
  14. 14Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
  15. 15Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  16. 16Institute of Medical Genetics, Cardiff University School of Medicine, Cardiff, UK
  17. 17Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
  18. 18Institute of Genetic Medicine Newcastle University, Newcastle upon Tyne, UK
  19. 19Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, Part of Oslo University Hospital, Oslo, Norway
  20. 20Department of Informatics, University of Oslo, Oslo, Norway
  21. 21Department of Mathematics and Statistics, Lancaster University, Lancaster, UK
  22. 22Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands
  23. 23Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK
  24. 24Department of Clinical Genetics and Department of Human Genetics Leiden University Medical Centre, Leiden, The Netherlands
  25. 25Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia
  26. 26Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
  27. 27Department of Biomedicine, Aarhus University, Aarhus, Denmark
  28. 28Division of Obstetrics and Gynecology, Department of Women's and Children's health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  29. 29Department of Surgery, Helsinki University Hospital, Helsinki, Finland
  30. 30Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland
  31. 31Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland
  32. 32Institute of Genomic Medicine, “A. Gemelli” Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy
  33. 33University of Eastern Finland, Jyvaskyla, Finland
  34. 34Surgical Center for Hereditary Tumors, HELIOS University Clinic Wuppertal, University Witten-Herdecke, Wuppertal, Germany
  1. Correspondence to Dr Pål Møller, Research Group Inherited Cancer, The Norwegian Radium Hospital, Oslo 0310, Norway; moller.pal{at}gmail.com

Abstract

Objective Today 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?

Design Information 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.

Results 1273 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%).

Conclusions Relative 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.

  • INHERITED CANCERS
  • EPIDEMIOLOGY
  • CANCER GENETICS
  • COLORECTAL CANCER GENES
  • SCREENING

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  • Abstract in Norwegian

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