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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • University of Oslo
  • University of Helsinki
  • Tampere University
  • University of Melbourne
  • Universität Heidelberg
  • Heidelberg Institute for Theoretical Studies
  • Aalborg University
  • Universität Aarhus
  • Universität Leipzig
  • Universität Bonn
  • Leiden University
  • University of Barcelona
  • University of Manchester
  • Newcastle University
  • Ludwig-Maximilians-Universität München (LMU)
  • MGZ - Medizinisch Genetisches Zentrum
  • IRCCS Istituto Europeo di Oncologia - Milano
  • Karolinska Institutet
  • Rabin Medical Center Israel
  • Royal Melbourne Hospital
  • University of Groningen
  • University of Parma
  • Hospital Fuerzas Armadas
  • Universität Basel
  • Rambam Health Care Campus Israel
  • Programa Cáncer Heredo Familiar Clínica Universidad de los Ande
  • University of Newcastle
  • Hebrew University of Jerusalem
  • Sheba Medical Center at Tel Hashomer
  • Hospital Italiano de Buenos Aires
  • Hospital A.C. Camargo
  • Tel Aviv University
  • Ben-Gurion University of the Negev
  • University College Dublin
  • Hospital Sirio-Libanes
  • University of Vermont
  • Universidad del Tolima
  • Foundation for Research in Genetics and Endocrinology (FRIGE)
  • University of Insubria
  • Instituto Nacional de Cancerologia
  • University of Zurich
  • Universidade Federal da Bahia
  • Hospital Privado Universitario de Córdoba


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.


Seiten (von - bis)1-11
FachzeitschriftHereditary cancer in clinical practice : the official journal of the Internationa
PublikationsstatusVeröffentlicht - Dez. 2022


Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete


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