Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Mev Dominguez-Valentin^#¹, Emma J Crosbie^#^{2

3}, Christoph Engel⁴, Stefan Aretz^{5

6}, Finlay Macrae^{7

8}, Ingrid Winship^{7

8}, Gabriel Capella⁹, Huw Thomas¹⁰, Sigve Nakken^{11

12}, Eivind Hovig^{11

13}, Maartje Nielsen¹⁴, Rolf H Sijmons¹⁵, Lucio Bertario^{16

17}, Bernardo Bonanni¹⁶, Maria Grazia Tibiletti¹⁸, Giulia Martina Cavestro¹⁹, Miriam Mints²⁰, Nathan Gluck^{21

22}, Lior Katz²³, Karl Heinimann²⁴, Carlos A Vaccaro^{25

26}, Kate Green²⁷, Fiona Lalloo²⁷, James Hill²⁸, Wolff Schmiegel²⁹, Deepak Vangala²⁹, Claudia Perne^{5

6}, Hans-Georg Strauß³⁰, Johanna Tecklenburg³¹, Elke Holinski-Feder^{32

33}, Verena Steinke-Lange^{32

33}, Jukka-Pekka Mecklin^{34

35}, John-Paul Plazzer³⁶, Marta Pineda³⁷, Matilde Navarro³⁷, Joan Brunet Vidal³⁷, Revital Kariv²², Guy Rosner²², Tamara Alejandra Piñero²⁶, María Laura Gonzalez²⁶, Pablo Kalfayan²⁶, Neil Ryan³⁸, Sanne W Ten Broeke¹⁵, Mark A Jenkins³⁹, Lone Sunde^{40

41}, Inge Bernstein^{42

43}, John Burn⁴⁴, Marc Greenblatt⁴⁵, Wouter H de Vos Tot Nederveen Cappel⁴⁶, Adriana Della Valle⁴⁷, Francisco Lopez-Koestner⁴⁸, Karin Alvarez⁴⁸, Reinhard Büttner⁴⁹, Heike Görgens⁵⁰, Monika Morak^{32

33}, Stefanie Holzapfel^{6

51}, Robert Hüneburg^{6

51}, Magnus von Knebel Doeberitz^{52

53}, Markus Loeffler⁴, Nils Rahner⁵⁴, Jürgen Weitz⁵⁰, Kirsi Pylvänäinen⁵⁵, Laura Renkonen-Sinisalo⁵⁶, Anna Lepistö⁵⁷, Annika Auranen⁵⁶, John L Hopper⁵⁸, Aung Ko Win³⁹, Robert W Haile⁵⁹, Noralane M Lindor⁵⁸, Steven Gallinger⁶⁰, Loïc Le Marchand⁶¹, Polly A Newcomb⁶², Jane C Figueiredo⁶², Stephen N Thibodeau⁶³, Christina Therkildsen⁶⁴, Henrik Okkels⁶⁵, Zohreh Ketabi⁶⁶, Oliver G Denton⁶⁷, Einar Andreas Rødland¹¹, Hans Vasen⁶⁸, Florencia Neffa⁴⁹, Patricia Esperon⁴⁹, Douglas Tjandra^{69

70}, Gabriela Möslein⁷¹, Julian R Sampson⁶⁷, D Gareth Evans^{72

73}, Toni T Seppälä^{74

75}, Pål Møller⁷⁶

Affiliations

¹ Department of Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. mev.dominguez.valentin@rr-research.no.
² Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and St Mary's Hospital, Manchester, UK. Emma.Crosbie@manchester.ac.uk.
³ Directorate of Gynaecology, Manchester University NHS Foundation Trust, Manchester, UK. Emma.Crosbie@manchester.ac.uk.
⁴ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁵ Institute of Human Genetics, University of Bonn, Bonn, Germany.
⁶ National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.
⁷ Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
⁸ Department of Medicine, Melbourne University, Melbourne, Australia.
⁹ Hereditary Cancer Program, Institut Catal. d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁰ St Mark's Hospital, Department of Surgery and Cancer, Imperial College London, London, UK.
¹¹ Department of Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
¹² Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹³ Department of Informatics, University of Oslo, Oslo, Norway.
¹⁴ Leids Universitair Medisch Centrum, Leiden, Netherlands.
¹⁵ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁶ IEO, European Institute of Oncology IRCCS, Milan, Italy.
¹⁷ Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
¹⁸ Ospedale di Circolo ASST Settelaghi, Centro di Ricerca tumori eredo-familiari, Università dell'Insubria, Varese, Italy.
¹⁹ Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
²⁰ Department of Women's and Children's health, Division of Obstetrics and Gyneacology, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
²¹ Tel-Aviv Sourasky Medical Center, Research Center for Digestive Disorders and Liver Diseases, Tel-Aviv, Israel.
²² Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
²³ High Risk and GI Cancer prevention Clinic, Gastro-Oncology Unit, The Department of Gastroenterology, Sheba Medical Center, Tel-Aviv, Israel.
²⁴ Medical Genetics, Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
²⁵ Hereditary Cancer Program (PROCANHE) Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
²⁶ Instituto de Ciencias Básicas y Medicina Experimental (ICBME)-Instituto Universitario (IU)-Hospital, Buenos Aires, Argentina.
²⁷ Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
²⁸ Department of Surgery, Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
²⁹ Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
³⁰ Department of Gynaecology, University Clinics, Martin-Luther University, Halle-Wittenberg, Germany.
³¹ Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
³² Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
³³ MGZ Medical Genetics Center, Munich, Germany.
³⁴ Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
³⁵ Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland.
³⁶ The Royal Melbourne Hospital, Melbourne, Australia.
³⁷ Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
³⁸ Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and St Mary's Hospital, Manchester, UK.
³⁹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
⁴⁰ Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark.
⁴¹ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
⁴² Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
⁴³ Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
⁴⁴ Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
⁴⁵ University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA.
⁴⁶ Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
⁴⁷ Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Hospital Fuerzas Armadas, Montevideo, Uruguay.
⁴⁸ Lab. Oncología y Genética Molecular, Unidad de coloproctología Clínica Las Condes, Santiago, Chile.
⁴⁹ Institute of Pathology, University of Cologne, Cologne, Germany.
⁵⁰ Department of Surgery, Technische Universität Dresden, Dresden, Germany.
⁵¹ Department of Internal Medicine I, University Hospital Bonn; National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.
⁵² Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁵³ Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵⁴ Institute of Human Genetics, Medical School, Heinrich Heine University, Duesseldorf, Germany.
⁵⁵ Department of Education and Science, Central Finland Health Care District, yväskylä, Finland.
⁵⁶ Department of Obstetrics and Gynecology and Tays Cancer Centre, Tampere University Hospital and Tampere University, Tampere, Finland.
⁵⁷ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Applied Tumour Genomics Research Program, University of Helsinki, Helsinki, Finland.
⁵⁸ Department of Health Science Research, Mayo Clinic Arizona, Phoenix, AZ, USA.
⁵⁹ Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, USA.
⁶⁰ Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
⁶¹ University of Hawaii Cancer Center, Honolulu, HI, USA.
⁶² Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁶³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁶⁴ The Danish HNPCC register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
⁶⁵ Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.
⁶⁶ Dept. of Obstetrics and Gynaecology, Copenhagen University Hospital, Rigshospitalet, Denmark.
⁶⁷ Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
⁶⁸ Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
⁶⁹ Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melborne, Australia.
⁷⁰ Department of Medicine, Melbourne University, Melborne, Australia.
⁷¹ Surgical Center for Hereditary Tumors, Ev. Bethesda Khs Duisburg, University Witten-Herdecke, Herdecke, Germany.
⁷² Division of Evolution and Genomic Medicine, University of Manchester, Manchester, UK.
⁷³ Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
⁷⁴ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
⁷⁵ Department of Surgical Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
⁷⁶ Department of Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. moller.pal@gmail.com.

^# Contributed equally.

PMID: 33257847
PMCID: PMC8026395
DOI: 10.1038/s41436-020-01029-1

Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Mev Dominguez-Valentin et al. Genet Med. 2021 Apr.

. 2021 Apr;23(4):705-712.

doi: 10.1038/s41436-020-01029-1. Epub 2020 Dec 1.

Authors

Affiliations

¹ Department of Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. mev.dominguez.valentin@rr-research.no.
² Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and St Mary's Hospital, Manchester, UK. Emma.Crosbie@manchester.ac.uk.
³ Directorate of Gynaecology, Manchester University NHS Foundation Trust, Manchester, UK. Emma.Crosbie@manchester.ac.uk.
⁴ Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
⁵ Institute of Human Genetics, University of Bonn, Bonn, Germany.
⁶ National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.
⁷ Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Australia.
⁸ Department of Medicine, Melbourne University, Melbourne, Australia.
⁹ Hereditary Cancer Program, Institut Catal. d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁰ St Mark's Hospital, Department of Surgery and Cancer, Imperial College London, London, UK.
¹¹ Department of Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
¹² Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹³ Department of Informatics, University of Oslo, Oslo, Norway.
¹⁴ Leids Universitair Medisch Centrum, Leiden, Netherlands.
¹⁵ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹⁶ IEO, European Institute of Oncology IRCCS, Milan, Italy.
¹⁷ Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
¹⁸ Ospedale di Circolo ASST Settelaghi, Centro di Ricerca tumori eredo-familiari, Università dell'Insubria, Varese, Italy.
¹⁹ Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy.
²⁰ Department of Women's and Children's health, Division of Obstetrics and Gyneacology, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden.
²¹ Tel-Aviv Sourasky Medical Center, Research Center for Digestive Disorders and Liver Diseases, Tel-Aviv, Israel.
²² Department of Gastroenterology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
²³ High Risk and GI Cancer prevention Clinic, Gastro-Oncology Unit, The Department of Gastroenterology, Sheba Medical Center, Tel-Aviv, Israel.
²⁴ Medical Genetics, Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
²⁵ Hereditary Cancer Program (PROCANHE) Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
²⁶ Instituto de Ciencias Básicas y Medicina Experimental (ICBME)-Instituto Universitario (IU)-Hospital, Buenos Aires, Argentina.
²⁷ Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
²⁸ Department of Surgery, Manchester University Hospitals NHS Foundation Trust and University of Manchester, Manchester, UK.
²⁹ Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
³⁰ Department of Gynaecology, University Clinics, Martin-Luther University, Halle-Wittenberg, Germany.
³¹ Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
³² Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
³³ MGZ Medical Genetics Center, Munich, Germany.
³⁴ Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
³⁵ Department of Surgery, Central Finland Health Care District, Jyväskylä, Finland.
³⁶ The Royal Melbourne Hospital, Melbourne, Australia.
³⁷ Hereditary Cancer Program, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
³⁸ Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester and St Mary's Hospital, Manchester, UK.
³⁹ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
⁴⁰ Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark.
⁴¹ Department of Biomedicine, Aarhus University, Aarhus, Denmark.
⁴² Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
⁴³ Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
⁴⁴ Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
⁴⁵ University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA.
⁴⁶ Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
⁴⁷ Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU), Hospital Fuerzas Armadas, Montevideo, Uruguay.
⁴⁸ Lab. Oncología y Genética Molecular, Unidad de coloproctología Clínica Las Condes, Santiago, Chile.
⁴⁹ Institute of Pathology, University of Cologne, Cologne, Germany.
⁵⁰ Department of Surgery, Technische Universität Dresden, Dresden, Germany.
⁵¹ Department of Internal Medicine I, University Hospital Bonn; National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.
⁵² Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁵³ Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵⁴ Institute of Human Genetics, Medical School, Heinrich Heine University, Duesseldorf, Germany.
⁵⁵ Department of Education and Science, Central Finland Health Care District, yväskylä, Finland.
⁵⁶ Department of Obstetrics and Gynecology and Tays Cancer Centre, Tampere University Hospital and Tampere University, Tampere, Finland.
⁵⁷ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, Applied Tumour Genomics Research Program, University of Helsinki, Helsinki, Finland.
⁵⁸ Department of Health Science Research, Mayo Clinic Arizona, Phoenix, AZ, USA.
⁵⁹ Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University, Stanford, USA.
⁶⁰ Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
⁶¹ University of Hawaii Cancer Center, Honolulu, HI, USA.
⁶² Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁶³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁶⁴ The Danish HNPCC register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
⁶⁵ Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.
⁶⁶ Dept. of Obstetrics and Gynaecology, Copenhagen University Hospital, Rigshospitalet, Denmark.
⁶⁷ Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, UK.
⁶⁸ Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
⁶⁹ Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melborne, Australia.
⁷⁰ Department of Medicine, Melbourne University, Melborne, Australia.
⁷¹ Surgical Center for Hereditary Tumors, Ev. Bethesda Khs Duisburg, University Witten-Herdecke, Herdecke, Germany.
⁷² Division of Evolution and Genomic Medicine, University of Manchester, Manchester, UK.
⁷³ Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
⁷⁴ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
⁷⁵ Department of Surgical Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
⁷⁶ Department of Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. moller.pal@gmail.com.

^# Contributed equally.

PMID: 33257847
PMCID: PMC8026395
DOI: 10.1038/s41436-020-01029-1

Abstract

Purpose: To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants.

Methods: The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages.

Results: Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively.

Conclusion: Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

PubMed Disclaimer

Conflict of interest statement

Reinhard Büttner: Co-founder and the chief scientific officer of Targos Mol Path Inc., Kassel, Germany. Sir Joh Burn: Has a patent for high speed low cost tumour profiling pending to John Burn and QuantuMDx.

Figures

Fig. 1. Survival when endometrial or ovarian cancer and cumulative risk by age for endometrial and/or ovarian cancer by pathogenic genetic variant. Whole line indicate point estimates, dotted lines indicate 95% confidence intervals.
a Survival of endometrial cancer and ovarian cancer by gene. b Cumulative incidences of endometrial or ovarian cancer by age and gene.

**Fig. 2**
Cumulative incidences of endometrial (to the right) or ovarian (to the left) cancer by age and genetic variant.

See this image and copyright information in PMC

References

1. Dominguez-Valentin M, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet. Med. 2019;22:15–25. doi: 10.1038/s41436-019-0596-9. - DOI - PMC - PubMed
1. Moller P, et al. Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database. Gut. 2017;66:1657–1664. doi: 10.1136/gutjnl-2016-311403. - DOI - PMC - PubMed
1. Moller 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;66:464–472. doi: 10.1136/gutjnl-2015-309675. - DOI - PMC - PubMed
1. Moller P, et al. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut. 2018;67:1306–1316. doi: 10.1136/gutjnl-2017-314057. - DOI - PMC - PubMed
1. Ryan NAJ, et al. Association of mismatch repair mutation with age at cancer onset in lynch syndrome: implications for stratified surveillance strategies. JAMA Oncol. 2017;3:1702–1706. doi: 10.1001/jamaoncol.2017.0619. - DOI - PMC - PubMed

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Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Affiliations

Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

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Conflict of interest statement

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