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Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database

Pål MøllerResearch Group Inherited Cancer, Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, NorwayToni T. SeppäläDepartment of Surgery, Central Finland Health Care District, Jyväskylä, FinlandInge BernsteinDanish HNPCC Register; Hvidovre University Hospital, Copenhagen, DenmarkElke Holinski‐FederMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Ziemssenstr. 1, Munich, GermanyPaola SalaUnit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori, Milan, ItalyD. Gareth EvansManchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UKAnnika LindblomDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, SwedenFinlay MacraeDepartment of Medicine, Melbourne University, Melbourne, AustraliaIgnacio BlancoInstitut Català d'OncologiaRolf H. SijmonsUniversity of GroningenJacqueline JeffriesInstitute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UKHans F. A. VasenDepartment of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The NetherlandsJohn BurnInstitute of Genetic Medicine Newcastle University, Newcastle upon Tyne, UKSigve NakkenDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, NorwayEivind HovigDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, NorwayEinar Andreas RødlandDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, NorwayKukatharmini TharmaratnamDepartment of Mathematics, University of Oslo, Oslo, NorwayWouter H. de Vos tot Nederveen CappelDepartment of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The NetherlandsJames HillDepartment of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UKJuul WijnenDepartment of Clinical Genetics and Department of Human Genetics Leiden University Medical Centre, Leiden, The NetherlandsKate GreenManchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UKFiona LallooManchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UKLone SundeDepartment of Clinical Genetics, Aarhus University Hospital, Aarhus, DenmarkMiriam MintsDivision of Obstetrics and Gynecology, Department of Women's and Children's health, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenLucio BertarioUnit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori, Milan, ItalyMarta PinedaHereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, SpainMatilde NavarroInstitut Català d'OncologiaMonika MorakMedizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Ziemssenstr. 1, Munich, GermanyLaura Renkonen‐SinisaloGenome-Scale Biology Research Program, University of Helsinki, Helsinki, FinlandIan M. FraylingInstitute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UKJohn‐Paul PlazzerColorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, AustraliaKirsi PylvänäinenDepartment of Education and Science, Central Finland Health Care District, Jyväskylä, FinlandJulian R. SampsonInstitute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UKGabriel CapelláHereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, SpainJukka‐Pekka MecklinCentral Finland Health Care DistrictGabriela MösleinDepartment of Surgery, HELIOS St Josefs Hospital Bochum-Linden (Helios), Bochum, Germany

2015en

ABI

Annotatsiya

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 http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.

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DOI: 10.1136/gutjnl-2015-309675

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