TY - JOUR T1 - Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database JF - Gut JO - Gut SP - 1657 LP - 1664 DO - 10.1136/gutjnl-2016-311403 VL - 66 IS - 9 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 - Mark Jenkins 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 - Maurizio Genuardi AU - Jukka-Pekka Mecklin AU - Gabriela Möslein AU - Julian R Sampson AU - Gabriel Capella AU - in collaboration with The Mallorca Group ( ) Y1 - 2017/09/01 UR - http://gut.bmj.com/content/66/9/1657.abstract N2 - Objective Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers?Design Information was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants.Results 1273 patients with LS from 10 countries were followed up for 7753 observation years. 318 patients (25.7%) developed 341 first subsequent cancers, including colorectal (n=147, 43%), upper GI, pancreas or bile duct (n=37, 11%) and urinary tract (n=32, 10%). The cumulative incidences for any subsequent cancer from age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year crude survival after CRC was 91% (95% CI 83% to 95%).Conclusions Relative incidence of subsequent cancer compared with incidence of first cancer was slightly but insignificantly higher than cancer incidence in patients with LS without previous cancer (range 0.94–1.49). The favourable survival after subsequent cancers validated continued follow-up to prevent death from cancer. The interactive website http://lscarisk.org was expanded to calculate the risks by gender, genetic variant and age for subsequent cancer for any patient with LS with previous cancer. ER -