Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance

First report from the prospective Lynch syndrome database

Pål Møller, Toni Seppälä, Inge Bernstein, Elke Holinski-Feder, Paola Sala, D. Gareth Evans, Annika Lindblom, Finlay Macrae, Ignacio Blanco, Rolf Sijmons, Jacqueline Jeffries, Hans Vasen, John Burn, Sigve Nakken, Eivind Hovig, Einar Andreas Rødland, Kukatharmini Tharmaratnam, Wouter H. de Vos tot Nederveen Cappel, James Hill, Juul Wijnen & 16 others Kate Green, Fiona Lalloo, Lone Sunde, Miriam Mints, Lucio Bertario, Marta Pineda, Matilde Navarro, Monika Morak, Laura Renkonen-Sinisalo, Ian M. Frayling, John Paul Plazzer, Kirsi Pylvanainen, Julian R. Sampson, Gabriel Capella, Jukka Pekka Mecklin, Gabriela Möslein

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Objective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. Design We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. Results 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian. Conclusions The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.

Original languageEnglish
JournalGut
DOIs
Publication statusAccepted/In press - Dec 9 2015

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Hereditary Nonpolyposis Colorectal Neoplasms
Databases
Survival
Incidence
Colorectal Neoplasms
Neoplasms
Mutation
Genes
Penetrance
Genetic Counseling
Endometrial Neoplasms
Ovarian Neoplasms
Multicenter Studies
Retrospective Studies
Observation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance : First report from the prospective Lynch syndrome database. / Møller, Pål; Seppälä, Toni; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Evans, D. Gareth; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rødland, Einar Andreas; Tharmaratnam, Kukatharmini; de Vos tot Nederveen Cappel, Wouter H.; Hill, James; Wijnen, Juul; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda, Marta; Navarro, Matilde; Morak, Monika; Renkonen-Sinisalo, Laura; Frayling, Ian M.; Plazzer, John Paul; Pylvanainen, Kirsi; Sampson, Julian R.; Capella, Gabriel; Mecklin, Jukka Pekka; Möslein, Gabriela.

In: Gut, 09.12.2015.

Research output: Contribution to journalArticle

Møller, P, Seppälä, T, Bernstein, I, Holinski-Feder, E, Sala, P, Evans, DG, Lindblom, A, Macrae, F, Blanco, I, Sijmons, R, Jeffries, J, Vasen, H, Burn, J, Nakken, S, Hovig, E, Rødland, EA, Tharmaratnam, K, de Vos tot Nederveen Cappel, WH, Hill, J, Wijnen, J, Green, K, Lalloo, F, Sunde, L, Mints, M, Bertario, L, Pineda, M, Navarro, M, Morak, M, Renkonen-Sinisalo, L, Frayling, IM, Plazzer, JP, Pylvanainen, K, Sampson, JR, Capella, G, Mecklin, JP & Möslein, G 2015, 'Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: First report from the prospective Lynch syndrome database', Gut. https://doi.org/10.1136/gutjnl-2015-309675
Møller, Pål ; Seppälä, Toni ; Bernstein, Inge ; Holinski-Feder, Elke ; Sala, Paola ; Evans, D. Gareth ; Lindblom, Annika ; Macrae, Finlay ; Blanco, Ignacio ; Sijmons, Rolf ; Jeffries, Jacqueline ; Vasen, Hans ; Burn, John ; Nakken, Sigve ; Hovig, Eivind ; Rødland, Einar Andreas ; Tharmaratnam, Kukatharmini ; de Vos tot Nederveen Cappel, Wouter H. ; Hill, James ; Wijnen, Juul ; Green, Kate ; Lalloo, Fiona ; Sunde, Lone ; Mints, Miriam ; Bertario, Lucio ; Pineda, Marta ; Navarro, Matilde ; Morak, Monika ; Renkonen-Sinisalo, Laura ; Frayling, Ian M. ; Plazzer, John Paul ; Pylvanainen, Kirsi ; Sampson, Julian R. ; Capella, Gabriel ; Mecklin, Jukka Pekka ; Möslein, Gabriela. / Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance : First report from the prospective Lynch syndrome database. In: Gut. 2015.
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title = "Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: First report from the prospective Lynch syndrome database",
abstract = "Objective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. Design We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. Results 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46{\%}, 35{\%}, 20{\%} and 10{\%} for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34{\%}, 51{\%}, 49{\%} and 24{\%}; and for ovarian cancer 11{\%}, 15{\%}, 0{\%} and 0{\%}. Ten-year crude survival was 87{\%} after any cancer, 91{\%} if the first cancer was colorectal, 98{\%} if endometrial and 89{\%} if ovarian. Conclusions The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.",
author = "P{\aa}l M{\o}ller and Toni Sepp{\"a}l{\"a} and Inge Bernstein and Elke Holinski-Feder and Paola Sala and Evans, {D. Gareth} and Annika Lindblom and Finlay Macrae and Ignacio Blanco and Rolf Sijmons and Jacqueline Jeffries and Hans Vasen and John Burn and Sigve Nakken and Eivind Hovig and R{\o}dland, {Einar Andreas} and Kukatharmini Tharmaratnam and {de Vos tot Nederveen Cappel}, {Wouter H.} and James Hill and Juul Wijnen and Kate Green and Fiona Lalloo and Lone Sunde and Miriam Mints and Lucio Bertario and Marta Pineda and Matilde Navarro and Monika Morak and Laura Renkonen-Sinisalo and Frayling, {Ian M.} and Plazzer, {John Paul} and Kirsi Pylvanainen and Sampson, {Julian R.} and Gabriel Capella and Mecklin, {Jukka Pekka} and Gabriela M{\"o}slein",
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T1 - Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance

T2 - First report from the prospective Lynch syndrome database

AU - Møller, Pål

AU - Seppälä, Toni

AU - Bernstein, Inge

AU - Holinski-Feder, Elke

AU - Sala, Paola

AU - Evans, D. Gareth

AU - Lindblom, Annika

AU - Macrae, Finlay

AU - Blanco, Ignacio

AU - Sijmons, Rolf

AU - Jeffries, Jacqueline

AU - Vasen, Hans

AU - Burn, John

AU - Nakken, Sigve

AU - Hovig, Eivind

AU - Rødland, Einar Andreas

AU - Tharmaratnam, Kukatharmini

AU - de Vos tot Nederveen Cappel, Wouter H.

AU - Hill, James

AU - Wijnen, Juul

AU - Green, Kate

AU - Lalloo, Fiona

AU - Sunde, Lone

AU - Mints, Miriam

AU - Bertario, Lucio

AU - Pineda, Marta

AU - Navarro, Matilde

AU - Morak, Monika

AU - Renkonen-Sinisalo, Laura

AU - Frayling, Ian M.

AU - Plazzer, John Paul

AU - Pylvanainen, Kirsi

AU - Sampson, Julian R.

AU - Capella, Gabriel

AU - Mecklin, Jukka Pekka

AU - Möslein, Gabriela

PY - 2015/12/9

Y1 - 2015/12/9

N2 - Objective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. Design We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. Results 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian. Conclusions The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.

AB - Objective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. Design We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. Results 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian. Conclusions The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.

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