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Multicenter Study
. 2017 Mar;66(3):464-472.
doi: 10.1136/gutjnl-2015-309675. Epub 2015 Dec 9.

Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database

Pål Møller  1 , Toni Seppälä  2 , Inge Bernstein  3   4 , Elke Holinski-Feder  5   6 , Paola Sala  7 , D Gareth Evans  8   9 , Annika Lindblom  10 , Finlay Macrae  11   12 , Ignacio Blanco  13 , Rolf Sijmons  14 , Jacqueline Jeffries  15 , Hans Vasen  16 , John Burn  17 , Sigve Nakken  18   19 , Eivind Hovig  18   19   20 , Einar Andreas Rødland  18 , Kukatharmini Tharmaratnam  21 , Wouter H de Vos Tot Nederveen Cappel  22 , James Hill  23 , Juul Wijnen  24 , Kate Green  8 , Fiona Lalloo  8 , Lone Sunde  3   25   26 , Miriam Mints  27 , Lucio Bertario  7 , Marta Pineda  13 , Matilde Navarro  13 , Monika Morak  5   6 , Laura Renkonen-Sinisalo  28   29 , Ian M Frayling  15 , John-Paul Plazzer  11 , Kirsi Pylvanainen  30 , Julian R Sampson  15 , Gabriel Capella  13 , Jukka-Pekka Mecklin  30   31 , Gabriela Möslein  32 ; Mallorca Group (http://mallorca-group.eu)
Affiliations
Multicenter Study

Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database

Pål Møller et al. Gut. 2017 Mar.

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.

Keywords: CANCER GENETICS; CANCER PREVENTION; CANCER SYNDROMES; COLONOSCOPY; COLORECTAL CANCER.

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Conflict of interest statement

Competing interests: JB has a patent for high-speed low-cost tumour profiling pending to JB and QuantuMDx. DGE is a NIHR senior investigator.

Figures

Figure 1
Figure 1
Calculated cumulative incidences by age and mutated gene for any cancer.
Figure 2
Figure 2
Calculated cumulative incidences by age and mutated gene for colorectal cancer (CRC) as the first cancer.
Figure 3
Figure 3
Calculated cumulative incidences by age and mutated gene for endometrial cancer as the first cancer by gene.
See this image and copyright information in PMC

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