TY - JOUR
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
AU - Mallorca Group (http://mallorca-group.eu)
N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
PY - 2017/3
Y1 - 2017/3
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.
U2 - 10.1136/gutjnl-2015-309675
DO - 10.1136/gutjnl-2015-309675
M3 - Journal article
C2 - 26657901
SN - 0017-5749
VL - 66
SP - 464
EP - 472
JO - Gut
JF - Gut
IS - 3
ER -