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

• Autores: Møller, Pål; Seppälä, Toni; Dowty, James G.; Haupt, Saskia; Dominguez Valentin, Mev; Sunde, Lone; Bernstein, Inge; Engel, Christoph; Aretz, Stefan; Nielsen, Maartje; Capella, Gabriel; Evans, Dafydd Gareth; Burn, John; Holinski Feder, Elke; Bertario, Lucio; Bonanni, Bernardo; Lindblom, Annika; Levi, Zohar; Macrae, Finlay; Winship, Ingrid; Plazzer, John Paul; Sijmons, Rolf; Laghi, Luigi; Valle, Adriana Della; Heinimann, Karl; Half, Elizabeth; Lopez Koestner, Francisco; Alvarez Valenzuela, Karin; Vaccaro, Carlos Alberto; Pavicic, Walter Hernan
• Año de publicación: 2022
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: COLONOSCOPY; COLORECTAL CANCER; EPIDEMIOLOGY; INCIDENCE; LYNCH SYNDROME; OVER-DIAGNOSIS; PENETRANCE; PREVENTION; PROSPECTIVE; SEGREGATION ANALYSIS
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Møller, Pål. The Norwegian Radium Hospital; Noruega
Fil: Seppälä, Toni. Universidad de Tampere; Finlandia. University of Helsinki; Finlandia
Fil: Dowty, James G.. University of Melbourne; Australia
Fil: Haupt, Saskia. Ruprecht Karls Universitat Heidelberg; Alemania. Heidelberg Institute for Theoretical Studies; Alemania
Fil: Dominguez Valentin, Mev. The Norwegian Radium Hospital; Noruega
Fil: Sunde, Lone. University Aarhus; Dinamarca. Aalborg University Hospital; Dinamarca
Fil: Bernstein, Inge. Aalborg University Hospital; Dinamarca
Fil: Engel, Christoph. Universitat Leipzig; Alemania
Fil: Aretz, Stefan. Universitat Bonn; Alemania
Fil: Nielsen, Maartje. Leids Universitair Medisch Centrum; Países Bajos
Fil: Capella, Gabriel. Institut Català d’Oncologia; España
Fil: Evans, Dafydd Gareth. University of Manchester; Reino Unido
Fil: Burn, John. University of Newcastle; Reino Unido
Fil: Holinski Feder, Elke. Klinikum der Universität München; Alemania. MGZ – Center of Medical Genetics; Alemania
Fil: Bertario, Lucio. European Institute of Oncology; Italia
Fil: Bonanni, Bernardo. European Institute of Oncology; Italia
Fil: Lindblom, Annika. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Levi, Zohar. Service High Risk GI Cancer Gastroenterology; Israel
Fil: Macrae, Finlay. University of Melbourne; Australia. The Royal Melbourne Hospital; Australia
Fil: Winship, Ingrid. University of Melbourne; Australia. The Royal Melbourne Hospital; Australia
Fil: Plazzer, John Paul. The Royal Melbourne Hospital; Australia
Fil: Sijmons, Rolf. University of Groningen; Países Bajos
Fil: Laghi, Luigi. Università di Parma; Italia
Fil: Valle, Adriana Della. Hospital Fuerzas Armadas; Uruguay
Fil: Heinimann, Karl. Universidad de Basilea; Suiza
Fil: Half, Elizabeth. Gastrointestinal Cancer Prevention Unit; Israel
Fil: Lopez Koestner, Francisco. Universidad de Los Andes; Chile
Fil: Alvarez Valenzuela, Karin. Universidad de Los Andes; Chile
Fil: Vaccaro, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentina
Fil: Pavicic, Walter Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentina