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 Pinero; Maria 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 Buettner; Heike Goergens; Monika Morak; Stefanie Holzapfel; Robert Hueneburg; Magnus von Knebel Doeberitz; Markus Loeffler; Nils Rahner; Jurgen Weitz; Kirsi Pylvanainen; Laura Renkonen-Sinisalo; Anna Lepisto; Annika Auranen; John L. Hopper; Aung Ko Win; Robert W. Haile; Noralane M. Lindor; Steven Gallinger; Loic Le Marchand; Polly A. Newcomb; Jane C. Figueiredo; Stephen N. Thibodeau; Christina Therkildsen; Henrik Okkels; Zohreh Ketabi; Oliver G. Denton; Einar Andreas Rodland; Hans Vasen; Florencia Neffa; Patricia Esperon; Douglas Tjandra; Gabriela Moeslein; Julian R. Sampson; D. Gareth Evans; Toni T. Seppala; Pal Moller

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 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 Pinero, Maria 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 Buettner, Heike Goergens, Monika Morak, Stefanie Holzapfel, Robert Hueneburg, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Jurgen Weitz, Kirsi Pylvanainen, Laura Renkonen-Sinisalo, Anna Lepisto, Annika Auranen, John L. Hopper, Aung Ko Win, Robert W. Haile, Noralane M. Lindor, Steven Gallinger, Loic Le Marchand, Polly A. Newcomb, Jane C. Figueiredo, Stephen N. Thibodeau, Christina Therkildsen, Henrik Okkels, Zohreh Ketabi, Oliver G. Denton, Einar Andreas Rodland, Hans Vasen, Florencia Neffa, Patricia Esperon, Douglas Tjandra, Gabriela Moeslein, Julian R. Sampson, D. Gareth Evans, Toni T. Seppala, Pal Moller

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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
Early online date	1-Dec-2020
DOIs	https://doi.org/10.1038/s41436-020-01029-1
Publication status	Published - Apr-2021

Keywords

HEREDITARY COLORECTAL-CANCER
ASPIRIN
CAPP2

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Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variantsFinal publisher's version, 609 KBLicence: CC BY

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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., ... Moller, 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{a17620baac574302a8cb2039d74d0895,

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.",

keywords = "HEREDITARY COLORECTAL-CANCER, ASPIRIN, CAPP2",

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 Hans-Georg Strauss and Johanna Tecklenburg and Elke Holinski-Feder and Verena Steinke-Lange and Jukka-Pekka Mecklin and John-Paul Plazzer and Marta Pineda and Matilde Navarro and \{Brunet Vidal\}, Joan and Revital Kariv and Guy Rosner and \{Alejandra Pinero\}, Tamara and \{Laura Gonzalez\}, Maria 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 Cappel, \{Wouter H. de Vos tot Nederveen\} and \{Della Valle\}, Adriana and Francisco Lopez-Koestner and Karin Alvarez and Reinhard Buettner and Heike Goergens and Monika Morak and Stefanie Holzapfel and Robert Hueneburg and Doeberitz, \{Magnus von Knebel\} and Markus Loeffler and Nils Rahner and Jurgen Weitz and Kirsi Pylvanainen and Laura Renkonen-Sinisalo and Anna Lepisto 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\}, Loic 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 Rodland, \{Einar Andreas\} and Hans Vasen and Florencia Neffa and Patricia Esperon and Douglas Tjandra and Gabriela Moeslein and Sampson, \{Julian R.\} and Evans, \{D. Gareth\} and Seppala, \{Toni T.\} and Pal Moller",

year = "2021",

month = apr,

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

language = "English",

volume = "23",

pages = "705--712",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Nature Publishing Group",

number = "4",

}

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, H-G, Tecklenburg, J, Holinski-Feder, E, Steinke-Lange, V, Mecklin, J-P, Plazzer, J-P, Pineda, M, Navarro, M, Brunet Vidal, J, Kariv, R, Rosner, G, Alejandra Pinero, T, Laura Gonzalez, M, Kalfayan, P, Ryan, N, Ten Broeke, SW, Jenkins, MA, Sunde, L, Bernstein, I, Burn, J, Greenblatt, M, Cappel, WHDVTN, Della Valle, A, Lopez-Koestner, F, Alvarez, K, Buettner, R, Goergens, H, Morak, M, Holzapfel, S, Hueneburg, R, Doeberitz, MVK, Loeffler, M, Rahner, N, Weitz, J, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, 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, Rodland, EA, Vasen, H, Neffa, F, Esperon, P, Tjandra, D, Moeslein, G, Sampson, JR, Evans, DG, Seppala, TT & Moller, 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 › Academic › 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 - Brunet Vidal, Joan

AU - Kariv, Revital

AU - Rosner, Guy

AU - Alejandra Pinero, Tamara

AU - Laura Gonzalez, Maria

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 - Cappel, Wouter H. de Vos tot Nederveen

AU - Della Valle, Adriana

AU - Lopez-Koestner, Francisco

AU - Alvarez, Karin

AU - Buettner, Reinhard

AU - Goergens, Heike

AU - Morak, Monika

AU - Holzapfel, Stefanie

AU - Hueneburg, Robert

AU - Doeberitz, Magnus von Knebel

AU - Loeffler, Markus

AU - Rahner, Nils

AU - Weitz, Jurgen

AU - Pylvanainen, Kirsi

AU - Renkonen-Sinisalo, Laura

AU - Lepisto, 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, Loic

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 - Rodland, Einar Andreas

AU - Vasen, Hans

AU - Neffa, Florencia

AU - Esperon, Patricia

AU - Tjandra, Douglas

AU - Moeslein, Gabriela

AU - Sampson, Julian R.

AU - Evans, D. Gareth

AU - Seppala, Toni T.

AU - Moller, Pal

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.

KW - HEREDITARY COLORECTAL-CANCER

KW - ASPIRIN

KW - CAPP2

U2 - 10.1038/s41436-020-01029-1

DO - 10.1038/s41436-020-01029-1

M3 - Article

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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