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. - PubMed - NCBI
Gut. 2017 Jul 28. doi: 10.1136/gutjnl-2017-314057. [Epub ahead of print]
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.
Møller P1,2,3,
Seppälä TT4,
Bernstein I5,6,
Holinski-Feder E7,8,
Sala P9,
Gareth Evans D10,11,
Lindblom A12,
Macrae F13,14,
Blanco I15,
Sijmons RH16,
Jeffries J17,
Vasen HFA18,
Burn J19,
Nakken S2,
Hovig E2,20,21,
Rødland EA2,
Tharmaratnam K22,
de Vos Tot Nederveen Cappel WH23,
Hill J24,
Wijnen JT25,
Jenkins MA26,
Green K10,11,
Lalloo F10,11,
Sunde L6,27,28,
Mints M29,
Bertario L9,
Pineda M15,
Navarro M15,
Morak M7,8,
Renkonen-Sinisalo L4,30,
Valentin MD1,2,
Frayling IM,
Plazzer JP13,
Pylvanainen K31,
Genuardi M32,
Mecklin JP33,
Moeslein G,
Sampson JR17,
Capella G15,3;
Mallorca Group.
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. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
KEYWORDS:
HNPCC syndrome; cancer prevention; clinical trials; colorectal cancer screening; inherited cancers
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