TY - JOUR

T1 - Colorectal cancer incidences in Lynch syndrome

T2 - a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

AU - Møller, Pål

AU - Seppälä, Toni

AU - Dowty, James G.

AU - Haupt, Saskia

AU - Dominguez-Valentin, Mev

AU - Sunde, Lone

AU - Bernstein, Inge

AU - Engel, Christoph

AU - Aretz, Stefan

AU - Nielsen, Maartje

AU - Capella, Gabriel

AU - Evans, Dafydd Gareth

AU - Burn, John

AU - Holinski-Feder, Elke

AU - Bertario, Lucio

AU - Bonanni, Bernardo

AU - Lindblom, Annika

AU - Levi, Zohar

AU - Macrae, Finlay

AU - Winship, Ingrid

AU - Plazzer, John Paul

AU - Sijmons, Rolf

AU - Laghi, Luigi

AU - Valle, Adriana Della

AU - Heinimann, Karl

AU - Half, Elizabeth

AU - Lopez-Koestner, Francisco

AU - Alvarez-Valenzuela, Karin

AU - Scott, Rodney J.

AU - Katz, Lior

AU - Laish, Ido

AU - Vainer, Elez

AU - Vaccaro, Carlos Alberto

AU - Carraro, Dirce Maria

AU - Gluck, Nathan

AU - Abu-Freha, Naim

AU - Stakelum, Aine

AU - Kennelly, Rory

AU - Winter, Des

AU - Rossi, Benedito Mauro

AU - Greenblatt, Marc

AU - Bohorquez, Mabel

AU - Sheth, Harsh

AU - Tibiletti, Maria Grazia

AU - Therkildsen, Christina

AU - Lindberg, Lars Joachim

AU - Gerdes, Anne Marie

AU - Wadt, Karin

AU - Rasmussen, Lene J.

AU - van Overeem Hansen, Thomas

AU - The European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC)

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Colonoscopy

KW - Colorectal cancer

KW - Epidemiology

KW - Incidence

KW - Lynch Syndrome

KW - Over-diagnosis

KW - Penetrance

KW - Prevention

KW - Prospective

KW - Segregation analysis

U2 - 10.1186/s13053-022-00241-1

DO - 10.1186/s13053-022-00241-1

M3 - Journal article

C2 - 36182917

AN - SCOPUS:85139440044

VL - 20

JO - Hereditary Cancer in Clinical Practice

JF - Hereditary Cancer in Clinical Practice

SN - 1731-2302

M1 - 36

ER -