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; Carlos 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

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^*, 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

Internal Medicine

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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 language	English
Pages (from-to)	705-712
Number of pages	8
Journal	Genetics in Medicine
Volume	23
Issue number	4
DOIs	https://doi.org/10.1038/s41436-020-01029-1
State	Published - Apr 2021

Funding

Funders	Funder number
Finnish Cancer Foundation
Wales Gene Park
Instrumentariumin Tiedesäätiö
Jane ja Aatos Erkon Säätiö
Centro de Investigación Biomédica en Red de Cáncer
Colon Cancer Family Registry
National Institute for Health Research
Ministerio de Economía y Competitividad
National Institutes of Health
Emil Aaltosen Säätiö
CCFR
Den Norske Kreftforening
Health and Care Research Wales
Suomen Lääketieteen Säätiö
Deutsche Krebshilfe
Sigrid Juséliuksen Säätiö
National Cancer Institute	U01CA074783, R01CA104132, U01CA167551, U24CA074794, U24CA074799, U01CA097735, U24CA074800, U01CA074806
Seattle Colorectal Cancer Family Registry	U01/U24 CA074794
University of Hawaii Colorectal Cancer Family Registry	R01 CA104132, U01/U24 CA074806
Australasian Colorectal Cancer Family Registry	U01/U24 CA097735, U01 CA074778
Kreftforeningen	194751–2017, 194751
USC Consortium Colorectal Cancer Family Registry	U01/U24 CA074799
European Regional Development Fund	SAF2015–68016-R
NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research	IS-BRC-1215–20007
Generalitat de Catalunya	2017SGR1282
Dutch Cancer Society	UL 2017-8223
Ontario Familial Colorectal Cancer Registry	U01/U24 CA074783
Mayo Clinic	NCI/NIH U01/U24 CA074800

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41436-020-01029-1

Cite this

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

@article{999e11653c0945868da74d6a99ef3629,

title = "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.",

author = "Mev Dominguez-Valentin and Crosbie, {Emma J.} and Christoph Engel and Stefan Aretz and Finlay Macrae and Ingrid Winship and Gabriel Capella and Huw Thomas and Sigve Nakken and Eivind Hovig and Maartje Nielsen and Sijmons, {Rolf H.} and Lucio Bertario and Bernardo Bonanni and Tibiletti, {Maria Grazia} and Cavestro, {Giulia Martina} and Miriam Mints and Nathan Gluck and Lior Katz and Karl Heinimann and Vaccaro, {Carlos A.} and Kate Green and Fiona Lalloo and James Hill and Wolff Schmiegel and Deepak Vangala and Claudia Perne and Strau{\ss}, {Hans Georg} and Johanna Tecklenburg and Elke Holinski-Feder and Verena Steinke-Lange and Mecklin, {Jukka Pekka} and Plazzer, {John Paul} and Marta Pineda and Matilde Navarro and Vidal, {Joan Brunet} and Revital Kariv and Guy Rosner and Pi{\~n}ero, {Tamara Alejandra} and Gonzalez, {Mar{\'i}a Laura} and Pablo Kalfayan and Neil Ryan and {ten Broeke}, {Sanne W.} and Jenkins, {Mark A.} and Lone Sunde and Inge Bernstein and John Burn and Marc Greenblatt and {de Vos tot Nederveen Cappel}, {Wouter H.} and {Della Valle}, Adriana and Francisco Lopez-Koestner and Karin Alvarez and Reinhard B{\"u}ttner and Heike G{\"o}rgens and Monika Morak and Stefanie Holzapfel and Robert H{\"u}neburg and {von Knebel Doeberitz}, Magnus and Markus Loeffler and Nils Rahner and J{\"u}rgen Weitz and Kirsi Pylv{\"a}n{\"a}inen and Laura Renkonen-Sinisalo and Anna Lepist{\"o} and Annika Auranen and Hopper, {John L.} and Win, {Aung Ko} and Haile, {Robert W.} and Lindor, {Noralane M.} and Steven Gallinger and {Le Marchand}, Lo{\"i}c and Newcomb, {Polly A.} and Figueiredo, {Jane C.} and Thibodeau, {Stephen N.} and Christina Therkildsen and Henrik Okkels and Zohreh Ketabi and Denton, {Oliver G.} and R{\o}dland, {Einar Andreas} and Hans Vasen and Florencia Neffa and Patricia Esperon and Douglas Tjandra and Gabriela M{\"o}slein and Sampson, {Julian R.} and Evans, {D. Gareth} and Sepp{\"a}l{\"a}, {Toni T.} and P{\aa}l M{\o}ller",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2021",

month = apr,

doi = "10.1038/s41436-020-01029-1",

language = "אנגלית",

volume = "23",

pages = "705--712",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Elsevier B.V.",

number = "4",

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Dominguez-Valentin, M, Crosbie, EJ, Engel, C, Aretz, S, Macrae, F, Winship, I, Capella, G, Thomas, H, Nakken, S, Hovig, E, Nielsen, M, Sijmons, RH, Bertario, L, Bonanni, B, Tibiletti, MG, Cavestro, GM, Mints, M, Gluck, N , Katz, L, Heinimann, K, Vaccaro, CA, Green, K, Lalloo, F, Hill, J, Schmiegel, W, Vangala, D, Perne, C, Strauß, HG, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, JP, Plazzer, JP, Pineda, M, Navarro, M, Vidal, JB, Kariv, R , Rosner, G, Piñero, TA, Gonzalez, ML, Kalfayan, P, Ryan, N, ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, de Vos tot Nederveen Cappel, WH, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Büttner, R, Görgens, H, Morak, M, Holzapfel, S, Hüneburg, R, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Weitz, J, Pylvänäinen, K, Renkonen-Sinisalo, L, Lepistö, A, Auranen, A, Hopper, JL, Win, AK, Haile, RW, Lindor, NM, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, JC, Thibodeau, SN, Therkildsen, C, Okkels, H, Ketabi, Z, Denton, OG, Rødland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Möslein, G, Sampson, JR, Evans, DG, Seppälä, TT & 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, vol. 23, no. 4, pp. 705-712. https://doi.org/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. / Dominguez-Valentin, Mev; Crosbie, Emma J.; Engel, Christoph et al.
In: Genetics in Medicine, Vol. 23, No. 4, 04.2021, p. 705-712.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants

T2 - a Prospective Lynch Syndrome Database report

AU - Dominguez-Valentin, Mev

AU - Crosbie, Emma J.

AU - Engel, Christoph

AU - Aretz, Stefan

AU - Macrae, Finlay

AU - Winship, Ingrid

AU - Capella, Gabriel

AU - Thomas, Huw

AU - Nakken, Sigve

AU - Hovig, Eivind

AU - Nielsen, Maartje

AU - Sijmons, Rolf H.

AU - Bertario, Lucio

AU - Bonanni, Bernardo

AU - Tibiletti, Maria Grazia

AU - Cavestro, Giulia Martina

AU - Mints, Miriam

AU - Gluck, Nathan

AU - Katz, Lior

AU - Heinimann, Karl

AU - Vaccaro, Carlos A.

AU - Green, Kate

AU - Lalloo, Fiona

AU - Hill, James

AU - Schmiegel, Wolff

AU - Vangala, Deepak

AU - Perne, Claudia

AU - Strauß, Hans Georg

AU - Tecklenburg, Johanna

AU - Holinski-Feder, Elke

AU - Steinke-Lange, Verena

AU - Mecklin, Jukka Pekka

AU - Plazzer, John Paul

AU - Pineda, Marta

AU - Navarro, Matilde

AU - Vidal, Joan Brunet

AU - Kariv, Revital

AU - Rosner, Guy

AU - Piñero, Tamara Alejandra

AU - Gonzalez, María Laura

AU - Kalfayan, Pablo

AU - Ryan, Neil

AU - ten Broeke, Sanne W.

AU - Jenkins, Mark A.

AU - Sunde, Lone

AU - Bernstein, Inge

AU - Burn, John

AU - Greenblatt, Marc

AU - de Vos tot Nederveen Cappel, Wouter H.

AU - Della Valle, Adriana

AU - Lopez-Koestner, Francisco

AU - Alvarez, Karin

AU - Büttner, Reinhard

AU - Görgens, Heike

AU - Morak, Monika

AU - Holzapfel, Stefanie

AU - Hüneburg, Robert

AU - von Knebel Doeberitz, Magnus

AU - Loeffler, Markus

AU - Rahner, Nils

AU - Weitz, Jürgen

AU - Pylvänäinen, Kirsi

AU - Renkonen-Sinisalo, Laura

AU - Lepistö, Anna

AU - Auranen, Annika

AU - Hopper, John L.

AU - Win, Aung Ko

AU - Haile, Robert W.

AU - Lindor, Noralane M.

AU - Gallinger, Steven

AU - Le Marchand, Loïc

AU - Newcomb, Polly A.

AU - Figueiredo, Jane C.

AU - Thibodeau, Stephen N.

AU - Therkildsen, Christina

AU - Okkels, Henrik

AU - Ketabi, Zohreh

AU - Denton, Oliver G.

AU - Rødland, Einar Andreas

AU - Vasen, Hans

AU - Neffa, Florencia

AU - Esperon, Patricia

AU - Tjandra, Douglas

AU - Möslein, Gabriela

AU - Sampson, Julian R.

AU - Evans, D. Gareth

AU - Seppälä, Toni T.

AU - Møller, Pål

PY - 2021/4

Y1 - 2021/4

N2 - 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.

AB - 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.

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U2 - 10.1038/s41436-020-01029-1

DO - 10.1038/s41436-020-01029-1

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C2 - 33257847

AN - SCOPUS:85096938751

SN - 1098-3600

VL - 23

SP - 705

EP - 712

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 4

ER -

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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