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 - Lino-Silva, Leonardo S.
AU - Horisberger, Karoline
AU - Portenkirchner, Carmen
AU - Nascimento, Ivana
AU - Kariv, Revital
AU - Rosner, Guy
AU - Rossi, Norma Teresa
AU - Chen-Shtoyerman, Rakefet
AU - da Silva, Leandro Apolinário
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
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
UR - http://www.scopus.com/inward/record.url?scp=85139440044&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13053-022-00241-1
DO - https://doi.org/10.1186/s13053-022-00241-1
M3 - مقالة
C2 - 36182917
SN - 1731-2302
VL - 20
JO - Hereditary Cancer in Clinical Practice
JF - Hereditary Cancer in Clinical Practice
IS - 1
M1 - 36
ER -