Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants : a Prospective Lynch Syndrome Database report
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.
Main Authors
Format
Articles
Research article
Published
2021
Series
Subjects
Publication in research information system
Publisher
Nature Publishing Group
The permanent address of the publication
https://urn.fi/URN:NBN:fi:jyu-202012036889Käytä tätä linkitykseen.
Review status
Peer reviewed
ISSN
1098-3600
DOI
https://doi.org/10.1038/s41436-020-01029-1
Language
English
Published in
Genetics in Medicine
Citation
- Dominguez-Valentin, M., Crosbie, E. J., Engel, C., Aretz, S., Macrae, F., Winship, I., Capella, G., Thomas, H., Nakken, S., Hovig, E., Nielsen, M., Sijmons, R. H., Bertario, L., Bonanni, B., Tibiletti, M. G., Cavestro, G. M., Mints, M., Gluck, N., Katz, L., . . . Møller, P. (2021). Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants : a Prospective Lynch Syndrome Database report. Genetics in Medicine, 23(4), 705-712. https://doi.org/10.1038/s41436-020-01029-1
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Additional information about funding
The study was supported by a Pink Ribbon grant (194751) from Den Norske Kreftforening to E.H. We express our gratitude to Heikki Järvinen, Beatrice Alcala-Repo, Teresa Ocaña, María Pellisé, Sabela Carballal, Liseth Rivero, Lorena Moreno, Gerhard Jung, Antoni Castells, Joaquin Cubiella, Laura Rivas, Luis Bujanda, Inés Gil, Jesús Bañales, Catalina Garau, Rodrigo Jover, María Dolores Picó, Xavier Bessa, Cristina Álvarez, Montserrat Andreu, Carmen Poves, Pedro Pérez Segura, Lucía Cid, Marta Carrillo, Enrique Quintero, Ángeles Pizarro, Marta Garzón, Adolfo Suárez, Inmaculada Salces, Daniel Rodriguez-Alcalde, Judith Balmaña, Adrià López, Nuria Dueñas, Gemma Llort, Carmen Yagüe, Teresa Ramón i Cajal, David Fisas Masferrer, Alexandra Gisbert Beamud, Consol López San Martín, Maite Herráiz, Pilar Pérez, Cristina Carretero, Maite Betés, 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).
Copyright© The Author(s) 2020