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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.
Gut. 2017 03; 66(3):464-472.Gut

Abstract

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.

Authors+Show Affiliations

Research Group Inherited Cancer, Department of Medical Genetics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland.Danish HNPCC Register; Hvidovre University Hospital, Copenhagen, Denmark. Department Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Ziemssenstr. 1, Munich, Germany. MGZ-Medizinisch Genetisches Zentrum, Munich, Germany.Unit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori, Milan, Italy.Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK.Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia. Department of Medicine, Melbourne University, Melbourne, Australia.Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK.Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.Institute of Genetic Medicine Newcastle University, Newcastle upon Tyne, UK.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 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.Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, part of Oslo University Hospital, Oslo, Norway.Department of Mathematics, University of Oslo, Oslo, Norway.Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.Department of Surgery, Central Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.Department of Clinical Genetics and Department of Human Genetics Leiden University Medical Centre, Leiden, The Netherlands.Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.Danish HNPCC Register; Hvidovre University Hospital, Copenhagen, Denmark. Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. Department of Biomedicine, Aarhus University, Aarhus, Denmark.Division of Obstetrics and Gynecology, Department of Women's and Children's health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.Unit of Hereditary Digestive Tract Tumors IRCCS Istituto Nazionale Tumori, Milan, Italy.Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Ziemssenstr. 1, Munich, Germany. MGZ-Medizinisch Genetisches Zentrum, Munich, Germany.Department of Surgery, Helsinki University Hospital, Helsinki, Finland. Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK.Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland.Institute of Medical Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK.Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.Department of Education and Science, Central Finland Health Care District, Jyväskylä, Finland. University of Eastern Finland, Jyväskylä, Finland.Department of Surgery, HELIOS St Josefs Hospital Bochum-Linden (Helios), Bochum, Germany.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26657901

Citation

Møller, Pål, et al. "Cancer Incidence and Survival in Lynch Syndrome Patients Receiving Colonoscopic and Gynaecological Surveillance: First Report From the Prospective Lynch Syndrome Database." Gut, vol. 66, no. 3, 2017, pp. 464-472.
Møller P, Seppälä T, Bernstein I, et al. Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2017;66(3):464-472.
Møller, P., Seppälä, T., Bernstein, I., Holinski-Feder, E., Sala, P., Evans, D. G., Lindblom, A., Macrae, F., Blanco, I., Sijmons, R., Jeffries, J., Vasen, H., Burn, J., Nakken, S., Hovig, E., Rødland, E. A., Tharmaratnam, K., de Vos Tot Nederveen Cappel, W. H., Hill, J., ... Möslein, G. (2017). Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut, 66(3), 464-472. https://doi.org/10.1136/gutjnl-2015-309675
Møller P, et al. Cancer Incidence and Survival in Lynch Syndrome Patients Receiving Colonoscopic and Gynaecological Surveillance: First Report From the Prospective Lynch Syndrome Database. Gut. 2017;66(3):464-472. PubMed PMID: 26657901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. AU - Møller,Pål, AU - Seppälä,Toni, AU - Bernstein,Inge, AU - Holinski-Feder,Elke, AU - Sala,Paola, AU - Evans,D Gareth, AU - Lindblom,Annika, AU - Macrae,Finlay, AU - Blanco,Ignacio, AU - Sijmons,Rolf, AU - Jeffries,Jacqueline, AU - Vasen,Hans, AU - Burn,John, AU - Nakken,Sigve, AU - Hovig,Eivind, AU - Rødland,Einar Andreas, AU - Tharmaratnam,Kukatharmini, AU - de Vos Tot Nederveen Cappel,Wouter H, AU - Hill,James, AU - Wijnen,Juul, AU - Green,Kate, AU - Lalloo,Fiona, AU - Sunde,Lone, AU - Mints,Miriam, AU - Bertario,Lucio, AU - Pineda,Marta, AU - Navarro,Matilde, AU - Morak,Monika, AU - Renkonen-Sinisalo,Laura, AU - Frayling,Ian M, AU - Plazzer,John-Paul, AU - Pylvanainen,Kirsi, AU - Sampson,Julian R, AU - Capella,Gabriel, AU - Mecklin,Jukka-Pekka, AU - Möslein,Gabriela, AU - ,, Y1 - 2015/12/09/ PY - 2015/03/27/received PY - 2015/11/06/revised PY - 2015/11/17/accepted PY - 2015/12/15/pubmed PY - 2017/7/8/medline PY - 2015/12/15/entrez KW - CANCER GENETICS KW - CANCER PREVENTION KW - CANCER SYNDROMES KW - COLONOSCOPY KW - COLORECTAL CANCER SP - 464 EP - 472 JF - Gut JO - Gut VL - 66 IS - 3 N2 - 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. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/26657901/Cancer_incidence_and_survival_in_Lynch_syndrome_patients_receiving_colonoscopic_and_gynaecological_surveillance:_first_report_from_the_prospective_Lynch_syndrome_database_ L2 - http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=26657901 DB - PRIME DP - Unbound Medicine ER -