Journal article

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 Heinimann Show all

Genetics in Medicine | SPRINGERNATURE | Published : 2020

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%..

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Grants

Awarded by Den Norske Kreftforening


Awarded by Norwegian Cancer Society


Awarded by Health and Care Research Wales through Wales Gene Park


Awarded by National Cancer Institute (NCI) of the National Institutes of Health (NIH)


Awarded by Dutch Cancer Society (DCS)


Awarded by Spanish Ministry of Economy and Competitiveness - FEDER funds (A Way to Build Europe)


Awarded by Government of Catalonia


Funding Acknowledgements

The study was supported by a Pink Ribbon grant (194751) from Den Norske Kreftforening to E.H. We express our gratitude to Heikki Jarvinen, Beatrice Alcala-Repo, Teresa Ocana, Maria Pellise, Sabela Carballal, Liseth Rivero, Lorena Moreno, Gerhard Jung, Antoni Castells, Joaquin Cubiella, Laura Rivas, Luis Bujanda, Ines Gil, Jesus Banales, Catalina Garau, Rodrigo Jover, Maria Dolores Pico, Xavier Bessa, Cristina Alvarez, Montserrat Andreu, Carmen Poves, Pedro Perez Segura, Lucia Cid, Marta Carrillo, Enrique Quintero, Angeles Pizarro, Marta Garzon, Adolfo Suarez, Inmaculada Salces, Daniel Rodriguez-Alcalde, Judith Balmana, Adria Lopez, Nuria Duenas, Gemma Llort, Carmen Yague, Teresa Ramon i Cajal, David Fisas Masferrer, Alexandra Gisbert Beamud, Consol Lopez San Martin, Maite Herraiz, Pilar Perez, Cristina Carretero, Maite Betes, Marta Ponce, Elena Aguirre, Nora Alfaro, Carlos Sarroca, and Marianne Haeusler for their efforts over many years. We also thank the Finnish Cancer Foundation, Jane and Aatos Erkko Foundation, Emil Aaltonen Foundation, Finnish Medical Foundation, Instrumentarium Science Foundation, Sigrid Juselius Foundation, and the Norwegian Cancer Society (contract 194751-2017) for funding. D.G.E. and E.J.C. are supported by the all Manchester National Institute for Health Research (NIHR) Biomedical Research Center (IS-BRC-1215-20007) and J.R.S. by Health and Care Research Wales through Wales Gene Park. N.R. was a Medical Research Council Doctoral Research Fellow (MR/M018431/1). Research reported in this publication was supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under award number UM1CA167551 and through cooperative agreements with the following The Colon Cancer Family Registry (CCFR) centers: Australasian Colorectal Cancer Family Registry (NCI/NIH U01 CA074778 and U01/U24 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (NCI/NIH U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (NCI/NIH U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (NCI/NIH U01/U24 CA074794), University of Hawaii Colorectal Cancer Family Registry (NCI/NIH U01/U24 CA074806 and R01 CA104132 to L.L.), USC Consortium Colorectal Cancer Family Registry (NCI/NIH U01/U24 CA074799). The German Consortium for Familial Intestinal Cancer has been supported by grants from the German Cancer Aid. Data collection from Wales, UK was supported by the Wales Gene Park. This work was cofunded by the European Regional Development Fund (ERDF). M.N. and S.W.t.B were supported by a grant from the Dutch Cancer Society (DCS), grant number UL 2017-8223. G.C., M.P., and J.B.V. were funded by the Spanish Ministry of Economy and Competitiveness and cofunded by FEDER funds (A Way to Build Europe) (grant SAF2015-68016-R), CIBERONC, the Government of Catalonia (grant 2017SGR1282).