RT Journal Article
SR Electronic
T1 Cancer risk and survival in <em>path_MMR</em> 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
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.