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

Mev Dominguez-Valentin*, Emma J. Crosbie*, Christoph Engel, Stefan Aretz, Finlay Macrae, Ingrid Winship, Gabriel Capella, Huw Thomas, Sigve Nakken, Eivind Hovig, Maartje Nielsen, Rolf H. Sijmons, Lucio Bertario, Bernardo Bonanni, Maria Grazia Tibiletti, Giulia Martina Cavestro, Miriam Mints, Nathan Gluck, Lior Katz, Karl HeinimannCarlos A. Vaccaro, Kate Green, Fiona Lalloo, James Hill, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Hans Georg Strauß, Johanna Tecklenburg, Elke Holinski-Feder, Verena Steinke-Lange, Jukka Pekka Mecklin, John Paul Plazzer, Marta Pineda, Matilde Navarro, Joan Brunet Vidal, Revital Kariv, Guy Rosner, Tamara Alejandra Piñero, María Laura Gonzalez, Pablo Kalfayan, Neil Ryan, Sanne W. ten Broeke, Mark A. Jenkins, Lone Sunde, Inge Bernstein, John Burn, Marc Greenblatt, Wouter H. de Vos tot Nederveen Cappel, Adriana Della Valle, Francisco Lopez-Koestner, Karin Alvarez, Reinhard Büttner, Heike Görgens, Monika Morak, Stefanie Holzapfel, Robert Hüneburg, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Jürgen Weitz, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepistö, Annika Auranen, John L. Hopper, Aung Ko Win, Robert W. Haile, Noralane M. Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane C. Figueiredo, Stephen N. Thibodeau, Christina Therkildsen, Henrik Okkels, Zohreh Ketabi, Oliver G. Denton, Einar Andreas Rødland, Hans Vasen, Florencia Neffa, Patricia Esperon, Douglas Tjandra, Gabriela Möslein, Julian R. Sampson, D. Gareth Evans, Toni T. Seppälä, Pål Møller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)705-712
Number of pages8
JournalGenetics in Medicine
Volume23
Issue number4
DOIs
StatePublished - Apr 2021

Funding

FundersFunder number
Australasian Colorectal Cancer Family RegistryU01 CA074778, U01/U24 CA097735
Biomedical Research CenterIS-BRC-1215–20007
CCFR
Colon Cancer Family Registry
Den Norske Kreftforening
Dutch Cancer SocietyUL 2017-8223
Finnish Cancer Foundation
Ontario Familial Colorectal Cancer RegistryU01/U24 CA074783
Seattle Colorectal Cancer Family RegistryU01/U24 CA074794
Sigrid Juselius Foundation
Spanish Ministry of Economy and Competitiveness
USC Consortium Colorectal Cancer Family RegistryU01/U24 CA074799
University of Hawaii Colorectal Cancer Family RegistryR01 CA104132, U01/U24 CA074806
Wales Gene Park
National Institutes of Health
National Cancer InstituteU24CA074794, UM1CA167551
National Cancer Institute
Mayo ClinicNCI/NIH U01/U24 CA074800
Mayo Clinic
Suomen Lääketieteen Säätiö
Kreftforeningen194751–2017, 194751
Kreftforeningen
Health and Care Research Wales
National Institute for Health Research
Generalitat de Catalunya2017SGR1282
Generalitat de Catalunya
Jane ja Aatos Erkon Säätiö
Emil Aaltosen Säätiö
Deutsche Krebshilfe
Instrumentariumin Tiedesäätiö
European Regional Development FundSAF2015–68016-R
European Regional Development Fund
Centro de Investigación Biomédica en Red de Cáncer

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