Journal
GUT
Volume 66, Issue 3, Pages 464-472Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/gutjnl-2015-309675
Keywords
-
Categories
Funding
- Finnish Cancer Foundation
- Sigrid Juselius Foundation
- Mary and Georg Ehrnrooth foundation
- Spanish Ministry of Economy and Competitiveness [SAF2012-33636]
- Carlos III Health Institute
- RTICC [RD12/0036/0008]
- Scientific Foundation Asociacion Espanola Contra el Cancer
- Government of Catalonia [2014 SGR 338]
- Welsh Contribution by the Wales Gene Park
- Cancer Research UK [15934] Funding Source: researchfish
- Medical Research Council [G0100496] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10214, NF-SI-0510-10282] Funding Source: researchfish
- MRC [G0100496] Funding Source: UKRI
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available