REVIEW

Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer)

H F A Vasen^1,*, G Möslein^2,*, A Alonso³, I Bernstein⁴, L Bertario⁵, I Blanco⁶, J Burn⁷, G Capella⁸, C Engel⁹, I Frayling¹⁰, W Friedl¹¹, F J Hes¹², S Hodgson¹³, J-P Mecklin¹⁴, P Møller¹⁵, F Nagengast¹⁶, Y Parc¹⁷, L Renkonen-Sinisalo¹⁸, J R Sampson¹⁰, A Stormorken¹⁹, J Wijnen¹²

¹ Department of Gastroenterology, Leiden University Medical Centre, Leiden, The Netherlands
² Department of Surgery, St Josefs Hospital Bochum-Linden (Helios), Bochum, Germany
³ Department of Medical Genetics, Hospital Virgen del Camino, Pamplona, Spain
⁴ Department of Gastroenterology, Hvidrove Hospital, Hvidrove, Denmark
⁵ Department of Surgery, Hospital Tumori, Milan, Italy
⁶ Department of Genetic Counselling, Prevention and Cancer, Catelonian Institute of Oncology, Barcelona, Spain
⁷ Institute of Human Genetics, Newcastle upon Tyne, UK
⁸ Translational Research Laboratory IDIBELL, Institut Catala D’Oncologia, Barcelona, Spain
⁹ Institute of Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
¹⁰ Institute of Medical Genetics, Cardiff, UK
¹¹ Institute of Human Genetics, University Clinics, Bonn, Germany
¹² Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
¹³ Department of Clinical Genetics, St George’s Hospital, London, UK
¹⁴ Department of Surgery, Jyvaskyla Central Hospital, Jyvaskyla, Finland
¹⁵ Department of Genetics, Norwegian Radium Hospital, Oslo, Norway
¹⁶ Department of Gastroenterology, University Medical Centre, Radboud, Nijmegen, The Netherlands
¹⁷ Department of Digestive Surgery, Hospital Saint-Antoine, University Pierre et Marie, Paris, France
¹⁸ Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
¹⁹ Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway

Correspondence to:
Dr H F A Vasen
Department of Gastroenterology, Leiden University Medical Centre & The Netherlands Foundation for the Detection of Hereditary Tumours, Rijnsburgerweg 10, 2333 AA Leiden, The Netherlands; hfavasen{at}stoet.nl

Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.

Abbreviations: CPT11, irinotecan; CRC, colorectal cancer; FAP, familial adenomatous polyposis; FU, fluorouracil; HNPCC, hereditary non-polyposis colorectal cancer; IHC, immunohistochemical; MSI, microsatellite instability; MMR, mismatch repair; QoL, quality of life; TVU, transvaginal ultrasound

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