title: Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database.
abstract: 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.
  
  
  
  We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affectingMLH1,MSH2,MSH6orPMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene.
  
  
  
  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 inMLH1andMSH2mutation carriers, and from about 40 years inMSH6andPMS2carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% forMLH1, MSH2, MSH6andPMS2mutation 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.
  
  
  
  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 http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.
authors.affiliation: Research Group Inherited Cancer, Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Møller
authors.affiliation: Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland.
authors.forename: Toni
authors.initials: T
authors.lastname: Seppälä
authors.affiliation: Danish HNPCC Register; Hvidovre University Hospital, Copenhagen, Denmark.|Department Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Inge
authors.initials: I
authors.lastname: Bernstein
authors.affiliation: Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Ziemssenstr. 1, Munich, Germany.|MGZ-Medizinisch Genetisches Zentrum, Munich, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.affiliation: Unit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Sala
authors.affiliation: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.|Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK.
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Lindblom
authors.affiliation: Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.|Department of Medicine, Melbourne University, Melbourne, Australia.
authors.forename: Finlay
authors.initials: F
authors.lastname: Macrae
authors.affiliation: Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ignacio
authors.identifier: 0000-0002-7414-7481
authors.initials: I
authors.lastname: Blanco
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sijmons
authors.affiliation: Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Jeffries
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Vasen
authors.affiliation: Institute of Genetic Medicine Newcastle University, Newcastle upon Tyne, UK.
authors.forename: John
authors.initials: J
authors.lastname: Burn
authors.affiliation: Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, Norway.|Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, Norway.
authors.forename: Sigve
authors.initials: S
authors.lastname: Nakken
authors.affiliation: Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, Norway.|Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, Norway.|Department of Informatics, University of Oslo, Oslo, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Hovig
authors.affiliation: Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, Norway.
authors.forename: Einar Andreas
authors.initials: EA
authors.lastname: Rødland
authors.affiliation: Department of Mathematics, University of Oslo, Oslo, Norway.
authors.forename: Kukatharmini
authors.initials: K
authors.lastname: Tharmaratnam
authors.affiliation: Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Wouter H
authors.initials: WH
authors.lastname: de Vos Tot Nederveen Cappel
authors.affiliation: Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hill
authors.affiliation: Department of Clinical Genetics and Department of Human Genetics Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Juul
authors.initials: J
authors.lastname: Wijnen
authors.affiliation: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Green
authors.affiliation: Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Lalloo
authors.affiliation: Danish HNPCC Register; Hvidovre University Hospital, Copenhagen, Denmark.|Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.|Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Sunde
authors.affiliation: Division of Obstetrics and Gynecology, Department of Women's and Children's health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Miriam
authors.initials: M
authors.lastname: Mints
authors.affiliation: Unit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Bertario
authors.affiliation: Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pineda
authors.affiliation: Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Ziemssenstr. 1, Munich, Germany.|MGZ-Medizinisch Genetisches Zentrum, Munich, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Morak
authors.affiliation: Department of Surgery, Helsinki University Hospital, Helsinki, Finland.|Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Renkonen-Sinisalo
authors.affiliation: Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Frayling
authors.affiliation: Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Plazzer
authors.affiliation: Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Pylvanainen
authors.affiliation: Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Sampson
authors.affiliation: Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.affiliation: Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.|University of Eastern Finland, Jyväskylä, Finland.
authors.forename: Jukka-Pekka
authors.initials: JP
authors.lastname: Mecklin
authors.affiliation: Department of Surgery, HELIOS St Josefs Hospital Bochum-Linden (Helios), Bochum, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Möslein
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003113:Colonoscopy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D004268:DNA-Binding Proteins / Q000235:genetics; D016208:Databases, Factual; D016889:Endometrial Neoplasms / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D051718:MutS Homolog 2 Protein / Q000235:genetics; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000401:mortality; D011159:Population Surveillance; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: CANCER GENETICS; CANCER PREVENTION; CANCER SYNDROMES; COLONOSCOPY; COLORECTAL CANCER