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The "unnatural" history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance

Lookup NU author(s): Dr Richard Gallon



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


© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control. Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alongside with hypotheses addressing colonoscopy quality and pace of progression from adenoma to cancer, we discuss the role of alternative precursors and immune system in LS-associated CRC. We also identify gaps in current knowledge and make suggestions for future studies aiming at improved CRC prevention for LS individuals.

Publication metadata

Author(s): Ahadova A, Seppala TT, Engel C, Gallon R, Burn J, Holinski-Feder E, Steinke-Lange V, Moslein G, Nielsen M, ten Broeke SW, Laghi L, Dominguez-Valentin M, Capella G, Macrae F, Scott R, Huneburg R, Nattermann J, Hoffmeister M, Brenner H, Blaker H, von Knebel Doeberitz M, Sampson JR, Vasen H, Mecklin J-P, Moller P, Kloor M

Publication type: Review

Publication status: Published

Journal: International Journal of Cancer

Year: 2021

Volume: 148

Issue: 4

Pages: 800-811

Print publication date: 15/02/2021

Online publication date: 19/07/2020

Acceptance date: 24/06/2020

ISSN (print): 0020-7136

ISSN (electronic): 1097-0215

Publisher: Wiley-Liss Inc.


DOI: 10.1002/ijc.33224

PubMed id: 32683684