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 (original) (raw)

Observational Study

. 2018 Jul;67(7):1306-1316.

doi: 10.1136/gutjnl-2017-314057. Epub 2017 Jul 28.

Pål Møller 1 2 3, Inge Bernstein 5 6, Elke Holinski-Feder 7 8, Paulo Sala 9, D Gareth Evans 10 11, Annika Lindblom 12, Finlay Macrae 13 14, Ignacio Blanco 15, Rolf H Sijmons 16, Jacqueline Jeffries 17, Hans F A Vasen 18, John Burn 19, Sigve Nakken 2, Eivind Hovig 2 20 21, Einar Andreas Rødland 2, Kukatharmini Tharmaratnam 22, Wouter H de Vos Tot Nederveen Cappel 23, James Hill 24, Juul T Wijnen 25, Mark A Jenkins 26, Kate Green 10 11, Fiona Lalloo 10 11, Lone Sunde 6 27 28, Miriam Mints 29, Lucio Bertario 9, Marta Pineda 15, Matilde Navarro 15, Monika Morak 7 8, Laura Renkonen-Sinisalo 4 30, Mev Dominguez Valentin 1 2, Ian M Frayling, John-Paul Plazzer 13, Kirsi Pylvanainen 31, Maurizio Genuardi [ 32](#full-view-affiliation-32 "Institute of Genomic Medicine, "A. Gemelli" Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy."), Jukka-Pekka Mecklin 33, Gabriela Moeslein, Julian R Sampson 17, Gabriel Capella 15 3; Mallorca Group

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Observational Study

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

Pål Møller et al. Gut. 2018 Jul.

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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.

Keywords: HNPCC syndrome; cancer prevention; clinical trials; colorectal cancer screening; inherited cancers.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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Conflict of interest statement

Competing interests: John Burn has a patent for high speed low cost tumour profiling pending to John Burn and QuantuMDx.

Figures

Figure 1

Figure 1

Cumulative incidences of colorectal cancer, upper gastrointestinal cancer (including stomach, duodenum, bile duct, gall bladder and pancreas) and urinary tract cancer (not including prostate).

Figure 2

Figure 2

Kaplan-Meier estimates of 10-year crude survival following colon cancer, sigmoid-rectal cancer, endometrial cancer or ovarian cancer that was diagnosed before 65 years of age after censoring for upper gastrointestinal or brain tumours. Solid line indicates point values; dotted lines indicate 95% CIs.

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