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

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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.

Originalsprog	Engelsk
Tidsskrift	Genetics In Medicine
ISSN	1098-3600
DOI	https://doi.org/10.1038/s41436-020-01029-1
Status	Udgivet - 1 dec. 2020

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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., ... Møller, P. (2020). Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report. Genetics In Medicine. https://doi.org/10.1038/s41436-020-01029-1

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, 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 2020, 'Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report', Genetics In Medicine. https://doi.org/10.1038/s41436-020-01029-1

@article{b256422d50d04aae9f89d13cedf6f7d5,

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 Hans-Georg Strau{\ss} 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 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",

year = "2020",

month = dec,

day = "1",

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

language = "English",

journal = "Genetics In Medicine",

issn = "1098-3600",

publisher = "Elsevier BV",

}

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 - 2020/12/1

Y1 - 2020/12/1

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.

UR - https://www.scopus.com/pages/publications/85096938751

U2 - 10.1038/s41436-020-01029-1

DO - 10.1038/s41436-020-01029-1

M3 - Journal article

C2 - 33257847

SN - 1098-3600

JO - Genetics In Medicine

JF - Genetics In Medicine

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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