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
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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.; Sampson, Julian R.; Sunde, Lone; Bernstein, Inge; Jenkins, Mark A.; Engel, Christoph; Aretz, Stefan; Nielsen, Maartje; Capella, Gabriel; Balaguer, Francesc; Evans, Dafydd Gareth; Burn, John; Holinski-Feder, Elke; Bertario, Lucio; Bonanni, Bernardo; Lindblom, Annika; Levi, Zohar; Macrae, Finlay; Winship, Ingrid; Plazzer, John Paul; Sijmons, Rolf; Laghi, Luigi; Della Valle, Adriana; Heinimann, Karl; Dębniak, Tadeusz; Fruscio, Robert; Lopez-Koestner, Francisco; Alvarez-Valenzuela, Karin; Katz, Lior H.; Laish, Ido; Vainer, Elez; Vaccaro, Carlos; Carraro, Dirce Maria; Monahan, Kevin; Half, Elizabeth; Stakelum, Aine; Winter, Des; Kennelly, Rory; Gluck, Nathan; Sheth, Harsh; Abu-Freha, Naim; Greenblatt, Marc; Rossi, Benedito Mauro; Bohorquez, Mabel; Cavestro, Giulia Martina; Lino-Silva, Leonardo S.; Horisberger, Karoline; Tibiletti, Maria Grazia; Nascimento, Ivana do; Thomas, Huw; Rossi, Norma Teresa; Apolinário da Silva, Leandro; Zaránd, Attila; Ruiz-Bañobre, Juan; Heuveline, Vincent; Mecklin, Jukka Pekka; Pylvänäinen, Kirsi; Renkonen-Sinisalo, Laura; Lepistö, Anna; Peltomäki, Päivi; Therkildsen, Christina; Madsen, Mia Gebauer; Burgdorf, Stefan Kobbelgaard; Hopper, John L.; Win, Aung Ko; Haile, Robert W.; Lindor, Noralane; Gallinger, Steven; Le Marchand, Loïc; Newcomb, Polly A.; Figueiredo, Jane; Buchanan, Daniel D.; Thibodeau, Stephen N.; von Knebel Doeberitz, Magnus; Loeffler, Markus; Rahner, Nils; Schröck, Evelin; Steinke-Lange, Verena; Schmiegel, Wolff; Vangala, Deepak; Perne, Claudia; Hüneburg, Robert; Redler, Silke; Büttner, Reinhard; Weitz, Jürgen; Pineda, Marta; Duenas, Nuria; Vidal, Joan Brunet; Moreira, Leticia; Sánchez, Ariadna; Hovig, Eivind; Nakken, Sigve; Green, Kate; Lalloo, Fiona; Hill, James; Crosbie, Emma; Mints, Miriam; Goldberg, Yael; Tjandra, Douglas; ten Broeke, Sanne W.; Kariv, Revital; Rosner, Guy; Advani, Suresh H.; Thomas, Lidiya; Shah, Pankaj; Shah, Mithun; Neffa, Florencia; Esperon, Patricia; Pavicic, Walter; Torrezan, Giovana Tardin; Bassaneze, Thiago; Martin, Claudia Alejandra; Moslein, Gabriela; Moller, Pål.
I: EClinicalMedicine, Bind 58, 101909, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2023
Y1 - 2023
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 - Mortality
KW - MSH2
KW - MSH6
KW - PMS2
KW - Prospective study
KW - Survival
U2 - 10.1016/j.eclinm.2023.101909
DO - 10.1016/j.eclinm.2023.101909
M3 - Journal article
C2 - 37181409
AN - SCOPUS:85153285119
VL - 58
JO - EClinicalMedicine
JF - EClinicalMedicine
SN - 2589-5370
M1 - 101909
ER -
ID: 365879756