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

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

*Corresponding author for this work

    Research output: Contribution to journalReview articleAcademicpeer-review

    14 Citations (Scopus)
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    Abstract

    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
    Volume148
    Issue number4
    Early online date3-Aug-2020
    DOIs
    Publication statusPublished - 15-Feb-2021

    Keywords

    • colonoscopy surveillance
    • colorectal cancer
    • incident cancer risk
    • Lynch syndrome
    • microsatellite instability
    • mismatch repair deficiency
    • MICROSATELLITE INSTABILITY
    • INTESTINAL MICROBIOTA
    • ADENOMA DETECTION
    • INTERVAL CANCERS
    • LONG-TERM
    • RISK
    • TUMORS
    • COLON
    • MANAGEMENT
    • MUTATION

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