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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

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  • Mev Dominguez-Valentin, Oslo Univ Hosp, University of Oslo, Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol
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  • Emma J. Crosbie, Manchester Univ NHS Fdn Trust, Directorate Gynaecol
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  • Christoph Engel, Univ Leipzig, University of Leipzig, Inst Med Informat Stat & Epidemiol
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  • Stefan Aretz, Univ Hosp Bonn, University of Bonn, Natl Ctr Hereditary Tumor Syndromes
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  • Finlay Macrae, Univ Melbourne, University of Melbourne, Royal Melbourne Hosp, Dept Med
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  • Ingrid Winship, Univ Melbourne, University of Melbourne, Royal Melbourne Hosp, Dept Med
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  • Gabriel Capella, Inst Catal Oncol IDIBELL, Catalan Institute of Oncology, Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), Hereditary Canc Program
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  • Huw Thomas, Imperial Coll London, Imperial College London, St Marks Hosp, Dept Surg & Canc
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  • Sigve Nakken, Univ Oslo, University of Oslo, Fac Med, Ctr Canc Cell Reprogramming, Inst Clin Med
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  • Eivind Hovig, Univ Oslo, University of Oslo, Dept Informat
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  • Maartje Nielsen, Leids Univ, Med Ctr
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  • Rolf H. Sijmons, Univ Groningen, University of Groningen, Univ Med Ctr Groningen, Dept Genet
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  • Lucio Bertario, Fdn IRCCS Ist Nazl Tumori, Fondazione IRCCS Istituto Nazionale Tumori Milan, Unit Immunotherapy Human Tumors
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  • Bernardo Bonanni, European Inst Oncol IRCCS, IRCCS European Institute of Oncology (IEO), IEO
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  • Maria Grazia Tibiletti, Univ Insubria, University of Insubria, Ctr Ric Tumori Eredofamiliari, Osped Circolo ASST Settelaghi
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  • Giulia Martina Cavestro, Univ Vita Salute San Raffaele, Vita-Salute San Raffaele University, San Raffaele Sci Inst, Gastroenterol & Gastrointestinal Endoscopy Unit
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  • Miriam Mints, Karolinska Univ Hosp, Karolinska Institutet, Karolinska University Hospital, Karolinska Inst, Dept Womens & Childrens Hlth, Div Obstet & Gyneacol
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  • Nathan Gluck, Tel Aviv Univ, Tel Aviv University, Sackler Faculty of Medicine, Sackler Fac Med
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  • Lior Katz, Sheba Med Ctr, Chaim Sheba Medical Center, Dept Gastroenterol, Gastrooncol Unit, High Risk & GI Canc Prevent Clin
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  • Karl Heinimann, Univ Hosp Basel, University of Basel, Inst Med Genet & Pathol
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  • Carlos A. Vaccaro, Inst Univ IU Hosp, Inst Ciencias Basicas & Med Expt ICBME
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  • Kate Green, Manchester Univ Hosp NHS Fdn Trust, Wythenshawe Hospital NHS Foundation Trust, Manchester Ctr Genom Med
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  • Fiona Lalloo, Manchester Univ Hosp NHS Fdn Trust, Wythenshawe Hospital NHS Foundation Trust, Manchester Ctr Genom Med
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  • James Hill, Univ Manchester, University of Manchester, Genom Med, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust
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  • Wolff Schmiegel, Ruhr Univ Bochum, Ruhr University Bochum, Dept Med, Knappschaftskrankenhaus
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  • Deepak Vangala, Ruhr Univ Bochum, Ruhr University Bochum, Dept Med, Knappschaftskrankenhaus
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  • Claudia Perne, Univ Hosp Bonn, University of Bonn, Natl Ctr Hereditary Tumor Syndromes
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  • Hans-Georg Strauss, Martin Luther Univ Halle Wittenberg, Martin Luther University Halle Wittenberg, Dept Gynaecol, Univ Clin
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  • Johanna Tecklenburg, Hannover Med Sch, Hannover Medical School, Inst Human Genet
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  • Elke Holinski-Feder, MGZ Med Genet Ctr
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  • Verena Steinke-Lange, MGZ Med Genet Ctr
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  • Jukka-Pekka Mecklin, Cent Finland Hlth Care Dist, Central Finland Central Hospital, Dept Surg
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  • John-Paul Plazzer, Univ Melbourne, Royal Children's Hospital Melbourne, University of Melbourne, Royal Childrens Hosp
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  • Marta Pineda, Inst Catala Oncol IDIBELL, Catalan Institute of Oncology, Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), Hereditary Canc Program
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  • Matilde Navarro, Inst Catala Oncol IDIBELL, Catalan Institute of Oncology, Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), Hereditary Canc Program
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  • Joan Brunet Vidal, Inst Catala Oncol IDIBELL, Catalan Institute of Oncology, Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), Hereditary Canc Program
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  • Revital Kariv, Tel Aviv Univ, Tel Aviv University, Sackler Faculty of Medicine, Sackler Fac Med
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  • Guy Rosner, Tel Aviv Univ, Tel Aviv University, Sackler Faculty of Medicine, Sackler Fac Med
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  • Tamara Alejandra Pinero, Inst Univ IU Hosp, Inst Ciencias Basicas & Med Expt ICBME
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  • Maria Laura Gonzalez, Inst Univ IU Hosp, Inst Ciencias Basicas & Med Expt ICBME
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  • Pablo Kalfayan, Inst Univ IU Hosp, Inst Ciencias Basicas & Med Expt ICBME
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  • Neil Ryan, St Marys Hosp, University of Manchester
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  • Sanne W. Ten Broeke, Univ Groningen, University of Groningen, Univ Med Ctr Groningen, Dept Genet
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  • Mark A. Jenkins, Univ Melbourne, University of Melbourne, Sch Populat & Global Hlth, Ctr Epidemiol & Biostat
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  • Lone Sunde
  • Inge Bernstein, Aalborg Univ Hosp, Aalborg University, Dept Surg Gastroenterol, Aalborg Univ Hosp, Aalborg University, Dept Clin Med
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  • John Burn, Newcastle Univ, Newcastle University - UK, Fac Med Sci
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  • Marc Greenblatt, Univ Vermont, University of Vermont, Robert Larner MD Coll Med, Dept Surg
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  • Wouter H. de Vos tot Nederveen Cappel, Isala Clin, Isala Clinics, Dept Gastroenterol & Hepatol
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  • Adriana Della Valle, Hosp Fuerzas Armadas, Grp Colaborat Uruguayo, Invest Afecc Oncol Gicas Hereditarias GCU
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  • Francisco Lopez-Koestner, Unidad Coloproctol Clin Las Condes, Lab Oncol & Genet Mol
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  • Karin Alvarez, Unidad Coloproctol Clin Las Condes, Lab Oncol & Genet Mol
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  • Reinhard Buettner, Univ Cologne, University of Cologne, Inst Pathol
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  • Heike Goergens, Tech Univ Dresden, Technische Universitat Dresden, Dept Surg
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  • Monika Morak, MGZ Med Genet Ctr
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  • Stefanie Holzapfel, Univ Hosp Bonn, University of Bonn, Dept Internal Med 1
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  • Robert Hueneburg, Univ Hosp Bonn, University of Bonn, Dept Internal Med 1
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  • Magnus von Knebel Doeberitz, German Canc Res Ctr, Helmholtz Association, German Cancer Research Center (DKFZ), Cooperat Unit Appl Tumour Biol
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  • Markus Loeffler, Univ Leipzig, University of Leipzig, Inst Med Informat Stat & Epidemiol
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  • Nils Rahner, Heinrich Heine Univ, Heinrich Heine University Dusseldorf, Inst Human Genet, Sch Med
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  • Jurgen Weitz, Tech Univ Dresden, Technische Universitat Dresden, Dept Surg
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  • Kirsi Pylvanainen, Univ Helsinki, University of Helsinki, Helsinki University Central Hospital, Helsinki Univ Cent Hosp, Dept Gastrointestinal Surg, Appl Tumour Genom Res Program
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  • Laura Renkonen-Sinisalo, Tampere Univ Hosp, University of Tampere
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  • Anna Lepisto, Univ Helsinki, University of Helsinki, Helsinki University Central Hospital, Helsinki Univ Cent Hosp, Dept Gastrointestinal Surg, Appl Tumour Genom Res Program
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  • Annika Auranen, Tampere Univ Hosp, University of Tampere
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  • John L. Hopper, Mayo Clin Arizona, Mayo Clinic, Mayo Clinic Phoenix, Dept Hlth Sci Res
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  • Aung Ko Win, Univ Melbourne, University of Melbourne, Sch Populat & Global Hlth, Ctr Epidemiol & Biostat
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  • Robert W. Haile, Stanford Univ, Stanford Cancer Institute, Stanford University, Stanford Canc Inst, Dept Med, Div Oncol
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  • Noralane M. Lindor, Mayo Clin Arizona, Mayo Clinic, Mayo Clinic Phoenix, Dept Hlth Sci Res
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  • Steven Gallinger, Univ Toronto, University of Toronto, Sinai Health System Toronto, Lunenfeld Tanenbaum Research Institute, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst
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  • Loic Le Marchand, Univ Hawaii, Cancer Research Center of Hawaii, University of Hawaii System, Canc Ctr
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  • Polly A. Newcomb, Fred Hutchinson Canc Res Ctr, Fred Hutchinson Cancer Center, Div Publ Hlth Sci, Program Epidemiol
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  • Jane C. Figueiredo, Fred Hutchinson Canc Res Ctr, Fred Hutchinson Cancer Center, Div Publ Hlth Sci, Program Epidemiol
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  • Stephen N. Thibodeau, Mayo Clin, Mayo Clinic, Dept Lab Med & Pathol, Div Expt Pathol
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  • Christina Therkildsen, Københavns Universitet
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  • Henrik Okkels, Aalborg Univ Hosp, Aalborg University, Dept Biochem, Sect Mol Diagnost
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  • Zohreh Ketabi, Københavns Universitet
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  • Oliver G. Denton, Cardiff Univ, Cardiff University, Sch Med, Inst Med Genet, Div Canc & Genet
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  • Einar Andreas Rodland, Oslo Univ Hosp, University of Oslo, Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol
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  • Hans Vasen, Leiden Univ, Leiden University, Leiden University Medical Center (LUMC), Dept Gastroenterol & Hepatol, Med Ctr
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  • Florencia Neffa, Univ Cologne, University of Cologne, Inst Pathol
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  • Patricia Esperon, Univ Cologne, University of Cologne, Inst Pathol
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  • Douglas Tjandra, Univ Melbourne, University of Melbourne, Royal Melbourne Hosp, Dept Med
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  • Gabriela Moeslein, Univ Witten Herdecke, Witten Herdecke University, Surg Ctr Hereditary Tumors, Ev Bethesda Khs Duisburg
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  • Julian R. Sampson, Cardiff Univ, Cardiff University, Sch Med, Inst Med Genet, Div Canc & Genet
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  • D. Gareth Evans, Univ Manchester, University of Manchester, Genom Med, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust
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  • Toni T. Seppala, Johns Hopkins Univ Hosp, Johns Hopkins University, Johns Hopkins Medicine, Dept Surg Oncol
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  • Pal Moller, Oslo Univ Hosp, University of Oslo, Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol

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.

OriginalsprogEngelsk
TidsskriftGenetics in Medicine
Vol/bind23
Nummer4
Sider (fra-til)705-712
Antal sider8
ISSN1098-3600
DOI
StatusUdgivet - apr. 2021

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