PT - JOURNAL ARTICLE AU - Pål Møller AU - Toni Seppälä AU - Inge Bernstein AU - Elke Holinski-Feder AU - Paola Sala AU - D Gareth Evans AU - Annika Lindblom AU - Finlay Macrae AU - Ignacio Blanco AU - Rolf Sijmons AU - Jacqueline Jeffries AU - Hans Vasen AU - John Burn AU - Sigve Nakken AU - Eivind Hovig AU - Einar Andreas Rødland AU - Kukatharmini Tharmaratnam AU - Wouter H de Vos tot Nederveen Cappel AU - James Hill AU - Juul Wijnen AU - Kate Green AU - Fiona Lalloo AU - Lone Sunde AU - Miriam Mints AU - Lucio Bertario AU - Marta Pineda AU - Matilde Navarro AU - Monika Morak AU - Laura Renkonen-Sinisalo AU - Ian M Frayling AU - John-Paul Plazzer AU - Kirsi Pylvanainen AU - Julian R Sampson AU - Gabriel Capella AU - Jukka-Pekka Mecklin AU - Gabriela Möslein AU - in collaboration with The Mallorca Group ( ) TI - Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database AID - 10.1136/gutjnl-2015-309675 DP - 2017 Mar 01 TA - Gut PG - 464--472 VI - 66 IP - 3 4099 - http://gut.bmj.com/content/66/3/464.short 4100 - http://gut.bmj.com/content/66/3/464.full SO - Gut2017 Mar 01; 66 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.