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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

Lookup NU author(s): Professor Sir John BurnORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

Abstract

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.

Publication metadata

Author(s): Møller P, Seppälä TT, Bernstein I, Holinski-Feder E, Sala P, Evans GD, Lindblom A, Macrae F, Blanco I, Sijmons RH, Jeffries J, Vasen HFA, Burn J, Nakken S, Hovig E, Rødland EA, Tharmaratnam K, de Vos tot Nederveen Cappel WH, Hill J, Wijnen JT, Jenkins MA, Green K, Lalloo F, Sunde L, Mints M, Bertario L, Pineda M, Navarro M, Morak M, Renkonen-Sinisalo L, Valentin MD, Frayling IM, Plazzer JP, Pylvanainen K, Genuardi M, Mecklin JP, Moeslein G, Sampson JR, Capella G

Publication type: Article

Publication status: Published

Journal: Gut

Year: 2018

Volume: 67

Issue: 7

Pages: 1306-1316

Print publication date: 01/07/2018

Online publication date: 28/07/2017

Acceptance date: 10/05/2017

Date deposited: 08/03/2018

ISSN (print): 0017-5749

ISSN (electronic): 1468-3288

Publisher: BMJ Group

URL: https://doi.org/10.1136/gutjnl-2017-314057

DOI: 10.1136/gutjnl-2017-314057

PubMed id: 28754778

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