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Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

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  • Pål Møller, University of Oslo
  • ,
  • Toni Seppälä, University of Helsinki, Tampere University
  • ,
  • James G. Dowty, University of Melbourne
  • ,
  • Saskia Haupt, Heidelberg University , Heidelberg Institute for Theoretical Studies
  • ,
  • Mev Dominguez-Valentin, University of Oslo
  • ,
  • Lone Sunde
  • Inge Bernstein, Aalborg University
  • ,
  • Christoph Engel, Leipzig University
  • ,
  • Stefan Aretz, University of Bonn
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  • Maartje Nielsen, Leiden University
  • ,
  • Gabriel Capella, University of Barcelona
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  • Dafydd Gareth Evans, Manchester University
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  • John Burn, Newcastle University
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  • Elke Holinski-Feder, Ludwig Maximilian University of Munich, MGZ- Medical Genetics Center
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  • Lucio Bertario, IRCCS Istituto Europeo di Oncologia - Milano
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  • Bernardo Bonanni, IRCCS Istituto Europeo di Oncologia - Milano
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  • Annika Lindblom, Karolinska Institutet
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  • Zohar Levi, Rabin Medical Center Israel
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  • Finlay Macrae, Royal Melbourne Hospital, University of Melbourne
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  • Ingrid Winship, Royal Melbourne Hospital, University of Melbourne
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  • John Paul Plazzer, Royal Melbourne Hospital
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  • Rolf Sijmons, University of Groningen
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  • Luigi Laghi, University of Parma
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  • Adriana Della Valle, Hospital Fuerzas Armadas
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  • The European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC)

Objective: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Original languageEnglish
Article number36
JournalHereditary Cancer in Clinical Practice
Volume20
Issue1
ISSN1731-2302
DOIs
Publication statusPublished - Dec 2022

    Research areas

  • Colonoscopy, Colorectal cancer, Epidemiology, Incidence, Lynch Syndrome, Over-diagnosis, Penetrance, Prevention, Prospective, Segregation analysis

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