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

Aysel Ahadova, Toni T. Seppälä, Christoph Engel, Richard Gallon, John Burn, Elke Holinski-Feder, Verena Steinke-Lange, Gabriela Möslein, Maartje Nielsen, Sanne W. ten Broeke, Luigi Laghi, Mev Dominguez-Valentin, Gabriel Capella, Finlay Macrae, Rodney Scott, Robert Hüneburg, Jacob Nattermann, Michael Hoffmeister, Hermann Brenner, Hendrik BläkerMagnus von Knebel Doeberitz, Julian R. Sampson, Hans Vasen, Jukka Pekka Mecklin, Pål Møller, Matthias Kloor

Research output: Contribution to journalReview Articlepeer-review

25 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)800-811
Number of pages12
JournalInternational journal of cancer
Issue number4
Publication statusPublished - 15 Feb 2021
Externally publishedYes
Publication typeA2 Review article in a scientific journal


  • colonoscopy surveillance
  • colorectal cancer
  • incident cancer risk
  • Lynch syndrome
  • microsatellite instability
  • mismatch repair deficiency

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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