Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database

Mev Dominguez-Valentin; Saskia Haupt; Toni T. Seppälä; Julian R. Sampson; Lone Sunde; Inge Bernstein; Mark A. Jenkins; Christoph Engel; Stefan Aretz; Maartje Nielsen; Gabriel Capella; Francesc Balaguer; Dafydd Gareth Evans; John Burn; Elke Holinski-Feder; Lucio Bertario; Bernardo Bonanni; Annika Lindblom; Zohar Levi; Finlay Macrae; Ingrid Winship; John Paul Plazzer; Rolf Sijmons; Luigi Laghi; Adriana Della Valle; Karl Heinimann; Tadeusz Dębniak; Robert Fruscio; Francisco Lopez-Koestner; Karin Alvarez-Valenzuela; Lior H. Katz; Ido Laish; Elez Vainer; Carlos Vaccaro; Dirce Maria Carraro; Kevin Monahan; Elizabeth Half; Aine Stakelum; Des Winter; Rory Kennelly; Nathan Gluck; Harsh Sheth; Naim Abu-Freha; Marc Greenblatt; Benedito Mauro Rossi; Mabel Bohorquez; Giulia Martina Cavestro; Leonardo S. Lino-Silva; Karoline Horisberger; Maria Grazia Tibiletti; Ivana do Nascimento; Huw Thomas; Norma Teresa Rossi; Leandro Apolinário da Silva; Attila Zaránd; Juan Ruiz-Bañobre; Vincent Heuveline; Jukka Pekka Mecklin; Kirsi Pylvänäinen; Laura Renkonen-Sinisalo; Anna Lepistö; Päivi Peltomäki; Christina Therkildsen; Mia Gebauer Madsen; Stefan Kobbelgaard Burgdorf; John L. Hopper; Aung Ko Win; Robert W. Haile; Noralane Lindor; Steven Gallinger; Loïc Le Marchand; Polly A. Newcomb; Jane Figueiredo; Daniel D. Buchanan; Stephen N. Thibodeau; Magnus von Knebel Doeberitz; Markus Loeffler; Nils Rahner; Evelin Schröck; Verena Steinke-Lange; Wolff Schmiegel; Deepak Vangala; Claudia Perne; Robert Hüneburg; Silke Redler; Reinhard Büttner; Jürgen Weitz; Marta Pineda; Nuria Duenas; Joan Brunet Vidal; Leticia Moreira; Ariadna Sánchez; Eivind Hovig; Sigve Nakken; Kate Green; Fiona Lalloo; James Hill; Emma Crosbie; Miriam Mints; Yael Goldberg; Douglas Tjandra; Sanne W. ten Broeke; Revital Kariv; Guy Rosner; Suresh H. Advani; Lidiya Thomas; Pankaj Shah; Mithun Shah; Florencia Neffa; Patricia Esperon; Walter Pavicic; Giovana Tardin Torrezan; Thiago Bassaneze; Claudia Alejandra Martin; Gabriela Moslein; Pål Moller

doi:10.1016/j.eclinm.2023.101909

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database

Mev Dominguez-Valentin, Saskia Haupt, Toni T. Seppälä, Julian R. Sampson, Lone Sunde, Inge Bernstein, Mark A. Jenkins, Christoph Engel, Stefan Aretz, Maartje Nielsen, Gabriel Capella, Francesc Balaguer, Dafydd Gareth Evans, John Burn, Elke Holinski-Feder, Lucio Bertario, Bernardo Bonanni, Annika Lindblom, Zohar Levi, Finlay MacraeIngrid Winship, John Paul Plazzer, Rolf Sijmons, Luigi Laghi, Adriana Della Valle, Karl Heinimann, Tadeusz Dębniak, Robert Fruscio, Francisco Lopez-Koestner, Karin Alvarez-Valenzuela, Lior H. Katz, Ido Laish, Elez Vainer, Carlos Vaccaro, Dirce Maria Carraro, Kevin Monahan, Elizabeth Half, Aine Stakelum, Des Winter, Rory Kennelly, Nathan Gluck, Harsh Sheth, Naim Abu-Freha, Marc Greenblatt, Benedito Mauro Rossi, Mabel Bohorquez, Giulia Martina Cavestro, Leonardo S. Lino-Silva, Karoline Horisberger, Maria Grazia Tibiletti, Ivana do Nascimento, Huw Thomas, Norma Teresa Rossi, Leandro Apolinário da Silva, Attila Zaránd, Juan Ruiz-Bañobre, Vincent Heuveline, Jukka Pekka Mecklin, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepistö, Päivi Peltomäki, Christina Therkildsen, Mia Gebauer Madsen, Stefan Kobbelgaard Burgdorf, John L. Hopper, Aung Ko Win, Robert W. Haile, Noralane Lindor, Steven Gallinger, Loïc Le Marchand, Polly A. Newcomb, Jane Figueiredo, Daniel D. Buchanan, Stephen N. Thibodeau, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Evelin Schröck, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Robert Hüneburg, Silke Redler, Reinhard Büttner, Jürgen Weitz, Marta Pineda, Nuria Duenas, Joan Brunet Vidal, Leticia Moreira, Ariadna Sánchez, Eivind Hovig, Sigve Nakken, Kate Green, Fiona Lalloo, James Hill, Emma Crosbie, Miriam Mints, Yael Goldberg, Douglas Tjandra, Sanne W. ten Broeke, Revital Kariv, Guy Rosner, Suresh H. Advani, Lidiya Thomas, Pankaj Shah, Mithun Shah, Florencia Neffa, Patricia Esperon, Walter Pavicic, Giovana Tardin Torrezan, Thiago Bassaneze, Claudia Alejandra Martin, Gabriela Moslein, Pål Moller

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

Abstract

Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.

Original language	English (US)
Article number	101909
Journal	EClinicalMedicine
Volume	58
DOIs	https://doi.org/10.1016/j.eclinm.2023.101909
State	Published - Apr 2023

Keywords

Cancer risk
Lynch syndrome
MLH1
MSH2
MSH6
Mortality
PMS2
Prospective study
Survival

ASJC Scopus subject areas

General Medicine

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Dominguez-Valentin, M., Haupt, S., Seppälä, T. T., Sampson, J. R., Sunde, L., Bernstein, I., Jenkins, M. A., Engel, C., Aretz, S., Nielsen, M., Capella, G., Balaguer, F., Evans, D. G., Burn, J., Holinski-Feder, E., Bertario, L., Bonanni, B., Lindblom, A., Levi, Z., ... Moller, P. (2023). Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database. EClinicalMedicine, 58, Article 101909. https://doi.org/10.1016/j.eclinm.2023.101909

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database. / Dominguez-Valentin, Mev; Haupt, Saskia; Seppälä, Toni T. et al.
In: EClinicalMedicine, Vol. 58, 101909, 04.2023.

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

Dominguez-Valentin, M, Haupt, S, Seppälä, TT, Sampson, JR, Sunde, L, Bernstein, I, Jenkins, MA, Engel, C, Aretz, S, Nielsen, M, Capella, G, Balaguer, F, Evans, DG, Burn, J, Holinski-Feder, E, Bertario, L, Bonanni, B, Lindblom, A, Levi, Z, Macrae, F, Winship, I, Plazzer, JP, Sijmons, R, Laghi, L, Della Valle, A, Heinimann, K, Dębniak, T, Fruscio, R, Lopez-Koestner, F, Alvarez-Valenzuela, K, Katz, LH, Laish, I, Vainer, E, Vaccaro, C, Carraro, DM, Monahan, K, Half, E, Stakelum, A, Winter, D, Kennelly, R, Gluck, N, Sheth, H, Abu-Freha, N, Greenblatt, M, Rossi, BM, Bohorquez, M, Cavestro, GM, Lino-Silva, LS, Horisberger, K, Tibiletti, MG, Nascimento, ID, Thomas, H, Rossi, NT, Apolinário da Silva, L, Zaránd, A, Ruiz-Bañobre, J, Heuveline, V, Mecklin, JP, Pylvänäinen, K, Renkonen-Sinisalo, L, Lepistö, A, Peltomäki, P, Therkildsen, C, Madsen, MG, Burgdorf, SK, Hopper, JL, Win, AK, Haile, RW, Lindor, N, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, J, Buchanan, DD, Thibodeau, SN, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Schröck, E, Steinke-Lange, V, Schmiegel, W, Vangala, D, Perne, C, Hüneburg, R, Redler, S, Büttner, R, Weitz, J, Pineda, M, Duenas, N, Vidal, JB, Moreira, L, Sánchez, A, Hovig, E, Nakken, S, Green, K, Lalloo, F, Hill, J, Crosbie, E, Mints, M, Goldberg, Y, Tjandra, D, ten Broeke, SW, Kariv, R, Rosner, G, Advani, SH, Thomas, L, Shah, P, Shah, M, Neffa, F, Esperon, P, Pavicic, W, Torrezan, GT, Bassaneze, T, Martin, CA, Moslein, G & Moller, P 2023, 'Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database', EClinicalMedicine, vol. 58, 101909. https://doi.org/10.1016/j.eclinm.2023.101909

@article{46abfbc729ac486bb276e7d4ed2da55a,

title = "Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database",

abstract = "Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.",

keywords = "Cancer risk, Lynch syndrome, MLH1, MSH2, MSH6, Mortality, PMS2, Prospective study, Survival",

author = "Mev Dominguez-Valentin and Saskia Haupt and Sepp{\"a}l{\"a}, {Toni T.} and Sampson, {Julian R.} and Lone Sunde and Inge Bernstein and Jenkins, {Mark A.} and Christoph Engel and Stefan Aretz and Maartje Nielsen and Gabriel Capella and Francesc Balaguer and Evans, {Dafydd Gareth} and John Burn and Elke Holinski-Feder and Lucio Bertario and Bernardo Bonanni and Annika Lindblom and Zohar Levi and Finlay Macrae and Ingrid Winship and Plazzer, {John Paul} and Rolf Sijmons and Luigi Laghi and {Della Valle}, Adriana and Karl Heinimann and Tadeusz D{\c e}bniak and Robert Fruscio and Francisco Lopez-Koestner and Karin Alvarez-Valenzuela and Katz, {Lior H.} and Ido Laish and Elez Vainer and Carlos Vaccaro and Carraro, {Dirce Maria} and Kevin Monahan and Elizabeth Half and Aine Stakelum and Des Winter and Rory Kennelly and Nathan Gluck and Harsh Sheth and Naim Abu-Freha and Marc Greenblatt and Rossi, {Benedito Mauro} and Mabel Bohorquez and Cavestro, {Giulia Martina} and Lino-Silva, {Leonardo S.} and Karoline Horisberger and Tibiletti, {Maria Grazia} and Nascimento, {Ivana do} and Huw Thomas and Rossi, {Norma Teresa} and {Apolin{\'a}rio da Silva}, Leandro and Attila Zar{\'a}nd and Juan Ruiz-Ba{\~n}obre and Vincent Heuveline and Mecklin, {Jukka Pekka} and Kirsi Pylv{\"a}n{\"a}inen and Laura Renkonen-Sinisalo and Anna Lepist{\"o} and P{\"a}ivi Peltom{\"a}ki and Christina Therkildsen and Madsen, {Mia Gebauer} and Burgdorf, {Stefan Kobbelgaard} and Hopper, {John L.} and Win, {Aung Ko} and Haile, {Robert W.} and Noralane Lindor and Steven Gallinger and {Le Marchand}, Lo{\"i}c and Newcomb, {Polly A.} and Jane Figueiredo and Buchanan, {Daniel D.} and Thibodeau, {Stephen N.} and {von Knebel Doeberitz}, Magnus and Markus Loeffler and Nils Rahner and Evelin Schr{\"o}ck and Verena Steinke-Lange and Wolff Schmiegel and Deepak Vangala and Claudia Perne and Robert H{\"u}neburg and Silke Redler and Reinhard B{\"u}ttner and J{\"u}rgen Weitz and Marta Pineda and Nuria Duenas and Vidal, {Joan Brunet} and Leticia Moreira and Ariadna S{\'a}nchez and Eivind Hovig and Sigve Nakken and Kate Green and Fiona Lalloo and James Hill and Emma Crosbie and Miriam Mints and Yael Goldberg and Douglas Tjandra and {ten Broeke}, {Sanne W.} and Revital Kariv and Guy Rosner and Advani, {Suresh H.} and Lidiya Thomas and Pankaj Shah and Mithun Shah and Florencia Neffa and Patricia Esperon and Walter Pavicic and Torrezan, {Giovana Tardin} and Thiago Bassaneze and Martin, {Claudia Alejandra} and Gabriela Moslein and P{\aa}l Moller",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = apr,

doi = "10.1016/j.eclinm.2023.101909",

language = "English (US)",

volume = "58",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Lancet Publishing Group",

}

TY - JOUR

T1 - Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment

T2 - a report from the prospective Lynch syndrome database

AU - Dominguez-Valentin, Mev

AU - Haupt, Saskia

AU - Seppälä, Toni T.

AU - Sampson, Julian R.

AU - Sunde, Lone

AU - Bernstein, Inge

AU - Jenkins, Mark A.

AU - Engel, Christoph

AU - Aretz, Stefan

AU - Nielsen, Maartje

AU - Capella, Gabriel

AU - Balaguer, Francesc

AU - Evans, Dafydd Gareth

AU - Burn, John

AU - Holinski-Feder, Elke

AU - Bertario, Lucio

AU - Bonanni, Bernardo

AU - Lindblom, Annika

AU - Levi, Zohar

AU - Macrae, Finlay

AU - Winship, Ingrid

AU - Plazzer, John Paul

AU - Sijmons, Rolf

AU - Laghi, Luigi

AU - Della Valle, Adriana

AU - Heinimann, Karl

AU - Dębniak, Tadeusz

AU - Fruscio, Robert

AU - Lopez-Koestner, Francisco

AU - Alvarez-Valenzuela, Karin

AU - Katz, Lior H.

AU - Laish, Ido

AU - Vainer, Elez

AU - Vaccaro, Carlos

AU - Carraro, Dirce Maria

AU - Monahan, Kevin

AU - Half, Elizabeth

AU - Stakelum, Aine

AU - Winter, Des

AU - Kennelly, Rory

AU - Gluck, Nathan

AU - Sheth, Harsh

AU - Abu-Freha, Naim

AU - Greenblatt, Marc

AU - Rossi, Benedito Mauro

AU - Bohorquez, Mabel

AU - Cavestro, Giulia Martina

AU - Lino-Silva, Leonardo S.

AU - Horisberger, Karoline

AU - Tibiletti, Maria Grazia

AU - Nascimento, Ivana do

AU - Thomas, Huw

AU - Rossi, Norma Teresa

AU - Apolinário da Silva, Leandro

AU - Zaránd, Attila

AU - Ruiz-Bañobre, Juan

AU - Heuveline, Vincent

AU - Mecklin, Jukka Pekka

AU - Pylvänäinen, Kirsi

AU - Renkonen-Sinisalo, Laura

AU - Lepistö, Anna

AU - Peltomäki, Päivi

AU - Therkildsen, Christina

AU - Madsen, Mia Gebauer

AU - Burgdorf, Stefan Kobbelgaard

AU - Hopper, John L.

AU - Win, Aung Ko

AU - Haile, Robert W.

AU - Lindor, Noralane

AU - Gallinger, Steven

AU - Le Marchand, Loïc

AU - Newcomb, Polly A.

AU - Figueiredo, Jane

AU - Buchanan, Daniel D.

AU - Thibodeau, Stephen N.

AU - von Knebel Doeberitz, Magnus

AU - Loeffler, Markus

AU - Rahner, Nils

AU - Schröck, Evelin

AU - Steinke-Lange, Verena

AU - Schmiegel, Wolff

AU - Vangala, Deepak

AU - Perne, Claudia

AU - Hüneburg, Robert

AU - Redler, Silke

AU - Büttner, Reinhard

AU - Weitz, Jürgen

AU - Pineda, Marta

AU - Duenas, Nuria

AU - Vidal, Joan Brunet

AU - Moreira, Leticia

AU - Sánchez, Ariadna

AU - Hovig, Eivind

AU - Nakken, Sigve

AU - Green, Kate

AU - Lalloo, Fiona

AU - Hill, James

AU - Crosbie, Emma

AU - Mints, Miriam

AU - Goldberg, Yael

AU - Tjandra, Douglas

AU - ten Broeke, Sanne W.

AU - Kariv, Revital

AU - Rosner, Guy

AU - Advani, Suresh H.

AU - Thomas, Lidiya

AU - Shah, Pankaj

AU - Shah, Mithun

AU - Neffa, Florencia

AU - Esperon, Patricia

AU - Pavicic, Walter

AU - Torrezan, Giovana Tardin

AU - Bassaneze, Thiago

AU - Martin, Claudia Alejandra

AU - Moslein, Gabriela

AU - Moller, Pål

PY - 2023/4

Y1 - 2023/4

N2 - Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.

AB - Background: The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time. Methods: The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender. Findings: Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers. Interpretation: In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome. Funding: We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.

KW - Cancer risk

KW - Lynch syndrome

KW - MLH1

KW - MSH2

KW - MSH6

KW - Mortality

KW - PMS2

KW - Prospective study

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=85153285119&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85153285119&partnerID=8YFLogxK

U2 - 10.1016/j.eclinm.2023.101909

DO - 10.1016/j.eclinm.2023.101909

M3 - Article

AN - SCOPUS:85153285119

SN - 2589-5370

VL - 58

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 101909

ER -

Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database

Abstract

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