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Original article
Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database
  1. Pål Møller1,
  2. Toni Seppälä2,
  3. Inge Bernstein3,4,
  4. Elke Holinski-Feder5,6,
  5. Paola Sala7,
  6. D Gareth Evans8,9,
  7. Annika Lindblom10,
  8. Finlay Macrae11,12,
  9. Ignacio Blanco13,
  10. Rolf Sijmons14,
  11. Jacqueline Jeffries15,
  12. Hans Vasen16,
  13. John Burn17,
  14. Sigve Nakken18,19,
  15. Eivind Hovig18,19,20,
  16. Einar Andreas Rødland18,
  17. Kukatharmini Tharmaratnam21,
  18. Wouter H de Vos tot Nederveen Cappel22,
  19. James Hill23,
  20. Juul Wijnen24,
  21. Kate Green8,
  22. Fiona Lalloo8,
  23. Lone Sunde3,25,26,
  24. Miriam Mints27,
  25. Lucio Bertario7,
  26. Marta Pineda13,
  27. Matilde Navarro13,
  28. Monika Morak5,6,
  29. Laura Renkonen-Sinisalo28,29,
  30. Ian M Frayling15,
  31. John-Paul Plazzer11,
  32. Kirsi Pylvanainen30,
  33. Julian R Sampson15,
  34. Gabriel Capella13,
  35. Jukka-Pekka Mecklin30,31,
  36. Gabriela Möslein32,
  37. in collaboration with The Mallorca Group (
  1. 1Research Group Inherited Cancer, Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  2. 2Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland
  3. 3Danish HNPCC Register; Hvidovre University Hospital, Copenhagen, Denmark
  4. 4Department Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
  5. 5Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Ziemssenstr. 1, Munich, Germany
  6. 6MGZ—Medizinisch Genetisches Zentrum, Munich, Germany
  7. 7Unit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori, Milan, Italy
  8. 8Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
  9. 9Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK
  10. 10Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
  11. 11Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia
  12. 12Department of Medicine, Melbourne University, Melbourne, Australia
  13. 13Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain
  14. 14Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
  15. 15Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK
  16. 16Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
  17. 17Institute of Genetic Medicine Newcastle University, Newcastle upon Tyne, UK
  18. 18Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, Norway
  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, University of Oslo, Oslo, Norway.
  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. 25Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
  26. 26Department of Biomedicine, Aarhus University, Aarhus, Denmark
  27. 27Division of Obstetrics and Gynecology, Department of Women's and Children's health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  28. 28Department of Surgery, Helsinki University Hospital, Helsinki, Finland
  29. 29Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland
  30. 30Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland
  31. 31University of Eastern Finland, Jyväskylä, Finland
  32. 32Department of Surgery, HELIOS St Josefs Hospital Bochum-Linden (Helios), Bochum, Germany
  1. Correspondence to Dr Pål Møller, Research Group Inherited Cancer, The Norwegian Radium Hospital, Oslo 0310, Norway; moller.pal{at}


Objective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance.

Design We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene.

Results 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian.

Conclusions The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.


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