RT Journal Article SR Electronic T1 Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1306 OP 1316 DO 10.1136/gutjnl-2017-314057 VO 67 IS 7 A1 Møller, Pål A1 Seppälä, Toni T A1 Bernstein, Inge A1 Holinski-Feder, Elke A1 Sala, Paulo A1 Gareth Evans, D A1 Lindblom, Annika A1 Macrae, Finlay A1 Blanco, Ignacio A1 Sijmons, Rolf H A1 Jeffries, Jacqueline A1 Vasen, Hans F A A1 Burn, John A1 Nakken, Sigve A1 Hovig, Eivind A1 Rødland, Einar Andreas A1 Tharmaratnam, Kukatharmini A1 de Vos tot Nederveen Cappel, Wouter H A1 Hill, James A1 Wijnen, Juul T A1 Jenkins, Mark A A1 Green, Kate A1 Lalloo, Fiona A1 Sunde, Lone A1 Mints, Miriam A1 Bertario, Lucio A1 Pineda, Marta A1 Navarro, Matilde A1 Morak, Monika A1 Renkonen-Sinisalo, Laura A1 Valentin, Mev Dominguez A1 Frayling, Ian M A1 Plazzer, John-Paul A1 Pylvanainen, Kirsi A1 Genuardi, Maurizio A1 Mecklin, Jukka-Pekka A1 Moeslein, Gabriela A1 Sampson, Julian R A1 Capella, Gabriel A1 , YR 2018 UL http://gut.bmj.com/content/67/7/1306.abstract AB Background Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival.Objective and design This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age.Results 3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer.Conclusion Carriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient’s age, gender and path_MMR variant. We have updated our open-access website www.lscarisk.org to facilitate this.