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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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 36 |
| Tidsskrift | Hereditary Cancer in Clinical Practice |
| Vol/bind | 20 |
| ISSN | 1731-2302 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
Toni T. Seppälä: Finnish Medical Foundation, Emil Aaltonen Foundation, Cancer Society Finland, Jane and Aatos Erkko Foundation, iCAN Digital Precision Cancer Medicine Flagship, Relander Foundation, Sigrid Juselius Foundation, and Academy of Finland. Jukka-Pekka Mecklin: Cancer Society Finland, Jane and Aatos Erkko Foundation. G Capellá team: funded by the Spanish Ministry of Economy and Competitiveness and co-funded by FEDER funds -a way to build Europe- (grant PID2019-111254RB-I00) and CIBERONC (CB16/12/00234). We thank CERCA Program / Generalitat de Catalunya for institutional support. S Aretz , E Holinski-Feder, and V Steinke-Lange were supported by the European Reference Network on Genetic Tumor Risk Syndromes (ERN GENTURIS) – Project ID No 739547. ERN GENTURIS is partly co-funded by the European Union within the framework of the Third Health Programme “ERN-2016 – Framework Partnership Agreement 2017–2021”. BMRossi team: we thank LA-GETH (Latin America - Grupo de Estudios de Tumores Hereditarios) for the Institutional support. DGE and EJC are supported by the all Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). JRS thanks HCRW for its support via Wales Gene Park. MRJ Kohonen-Corish had a grant from Cancer Council NSW grant RG19-01. J Burn contributed with support from Cancer Research U.K. catalyst award: Aspirin for Cancer Prevention AsCaP CRUK A24991. ”. The German Consortium for Familial Intestinal Cancer was supported by grants of the German Cancer Aid. DM Carraro and GT Torrezan: Funded by the National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (FAPESP 2014/509443-1, CNPq 465682/2014-6 and CAPES - 88887.136405/2017-00). ). We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.
Funding Information:
Harsh Sheth contributed with support from Gujarat State Biotechnology Mission grant GSBTM/JD(R&D)/604/2018-2019/7 and clinical oncologists Prof. Suresh h Advani, Dr. Pankaj Shah and Dr. Abhinav Jain. ERN GENTURIS is partly co-funded by the European Union within the framework of the Third Health Programme “ERN-2016 – Framework Partnership Agreement 2017–2021”. Funding bodies had no role in the study design, collection, analysis or interpretation of the data.
Publisher Copyright:
© 2022, The Author(s).
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