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

P. Møller; T. Seppälä; J. G. Dowty; S. Haupt; M. Dominguez-Valentin; L. Sunde; I. Bernstein; C. Engel; S. Aretz; M. Nielsen; G. Capella; D. G. Evans; J. Burn; E. Holinski-Feder; L. Bertario; B. Bonanni; A. Lindblom; Z. Levi; F. Macrae; I. Winship; J. -P. Plazzer; R. Sijmons; L. Laghi; A. D. Valle; K. Heinimann; E. Half; F. Lopez-Koestner; K. Alvarez-Valenzuela; R. J. Scott; L. Katz; I. Laish; E. Vainer; C. A. Vaccaro; D. M. Carraro; N. Gluck; N. Abu-Freha; A. Stakelum; R. Kennelly; D. Winter; B. M. Rossi; M. Greenblatt; M. Bohorquez; H. Sheth; M. G. Tibiletti; L. S. Lino-Silva; K. Horisberger; C. Portenkirchner; I. Nascimento; N.T. Rossi; L. Apolinário da Silva; H. Thomas; A. Zaránd; J. -P. Mecklin; K. Pylvänäinen; L. Renkonen-Sinisalo; A. Lepisto; P. Peltomäki; C. Therkildsen; L. J. Lindberg; O. Thorlacius-Ussing; M. Knebel Doeberitz; M. Loeffler; N. Rahner; V. Steinke-Lange; W. Schmiegel; D. Vangala; C. Perne; R. Hüneburg; A. Falcón de Vargas; A. Latchford; A. -M. Gerdes; A. -S. Backman; C. Guillén-Ponce; C. Snyder; C. K. Lautrup; D. Amor; E. Palmero; E. Stoffel; F. Duijkers; M. J. Hall; H. Hampel; H. Williams; H. Okkels; J. Lubiński; J. Reece; J. Ngeow; J. G. Guillem; J. Arnold; K. Wadt; K. Monahan; L. Senter; L. J. Rasmussen; L. P. van Hest; L. Ricciardiello; Maija R. J. Kohonen-Corish; M. J. L. Ligtenberg; M. Southey; M. Aronson; M. N. Zahary; N. J. Samadder; N. Poplawski; N. Hoogerbrugge; P. J. Morrison; P. James; G. Lee; R. Chen-Shtoyerman; R. Ankathil; R. Pai; R. Ward; S. Parry; T. Dębniak; T. John; T. van Overeem Hansen; T. Caldés; T. Yamaguchi; V. Barca-Tierno; P. Garre; G. M. Cavestro; J. Weitz; S. Redler; R. Büttner; V. Heuveline; J. L. Hopper; A. K. Win; N. Lindor; S. Gallinger; L. Le Marchand; P. A. Newcomb; J. Figueiredo; D. D. Buchanan; S. N. Thibodeau; S. W. Broeke; E. Hovig; S. Nakken; M. Pineda; N. Dueñas; J. Brunet; K. Green; F. Lalloo; K. Newton; E. J. Crosbie; M. Mints; D. Tjandra; F. Neffa; P. Esperon; R. Kariv; G. Rosner; W. H. Pavicic; P. Kalfayan; G. T. Torrezan; T. Bassaneze; C. Martin; G. Moslein; A. Ahadova; M. Kloor; J. R. Sampson; M. A. Jenkins; null The European Hereditary Tumour Group (EHTG); null International Mismatch Repair Consortium (IMRC)

doi:10.1186/s13053-022-00241-1

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

P. Møller, T. Seppälä, J. G. Dowty, S. Haupt, M. Dominguez-Valentin, L. Sunde, I. Bernstein, C. Engel, S. Aretz, M. Nielsen, G. Capella, D. G. Evans, J. Burn, E. Holinski-Feder, L. Bertario, B. Bonanni, A. Lindblom, Z. Levi, F. Macrae, I. WinshipJ. -P. Plazzer, R. Sijmons, L. Laghi, A. D. Valle, K. Heinimann, E. Half, F. Lopez-Koestner, K. Alvarez-Valenzuela, R. J. Scott, L. Katz, I. Laish, E. Vainer, C. A. Vaccaro, D. M. Carraro, N. Gluck, N. Abu-Freha, A. Stakelum, R. Kennelly, D. Winter, B. M. Rossi, M. Greenblatt, M. Bohorquez, H. Sheth, M. G. Tibiletti, L. S. Lino-Silva, K. Horisberger, C. Portenkirchner, I. Nascimento, N.T. Rossi, L. Apolinário da Silva, H. Thomas, A. Zaránd, J. -P. Mecklin, K. Pylvänäinen, L. Renkonen-Sinisalo, A. Lepisto, P. Peltomäki, C. Therkildsen, L. J. Lindberg, O. Thorlacius-Ussing, M. Knebel Doeberitz, M. Loeffler, N. Rahner, V. Steinke-Lange, W. Schmiegel, D. Vangala, C. Perne, R. Hüneburg, A. Falcón de Vargas, A. Latchford, A. -M. Gerdes, A. -S. Backman, C. Guillén-Ponce, C. Snyder, C. K. Lautrup, D. Amor, E. Palmero, E. Stoffel, F. Duijkers, M. J. Hall, H. Hampel, H. Williams, H. Okkels, J. Lubiński, J. Reece, J. Ngeow, J. G. Guillem, J. Arnold, K. Wadt, K. Monahan, L. Senter, L. J. Rasmussen, L. P. van Hest, L. Ricciardiello, Maija R. J. Kohonen-Corish, M. J. L. Ligtenberg, M. Southey, M. Aronson, M. N. Zahary, N. J. Samadder, N. Poplawski, N. Hoogerbrugge, P. J. Morrison, P. James, G. Lee, R. Chen-Shtoyerman, R. Ankathil, R. Pai, R. Ward, S. Parry, T. Dębniak, T. John, T. van Overeem Hansen, T. Caldés, T. Yamaguchi, V. Barca-Tierno, P. Garre, G. M. Cavestro, J. Weitz, S. Redler, R. Büttner, V. Heuveline, J. L. Hopper, A. K. Win, N. Lindor, S. Gallinger, L. Le Marchand, P. A. Newcomb, J. Figueiredo, D. D. Buchanan, S. N. Thibodeau, S. W. Broeke, E. Hovig, S. Nakken, M. Pineda, N. Dueñas, J. Brunet, K. Green, F. Lalloo, K. Newton, E. J. Crosbie, M. Mints, D. Tjandra, F. Neffa, P. Esperon, R. Kariv, G. Rosner, W. H. Pavicic, P. Kalfayan, G. T. Torrezan, T. Bassaneze, C. Martin, G. Moslein, A. Ahadova, M. Kloor, J. R. Sampson, M. A. Jenkins, The European Hereditary Tumour Group (EHTG), International Mismatch Repair Consortium (IMRC)

Western Sydney University

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	36
Number of pages	11
Journal	Hereditary Cancer in Clinical Practice
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s13053-022-00241-1
Publication status	Published - 2022

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Møller, P., Seppälä, T., Dowty, J. G., Haupt, S., Dominguez-Valentin, M., Sunde, L., Bernstein, I., Engel, C., Aretz, S., Nielsen, M., Capella, G., Evans, D. G., Burn, J., Holinski-Feder, E., Bertario, L., Bonanni, B., Lindblom, A., Levi, Z., Macrae, F., ... International Mismatch Repair Consortium (IMRC) (2022). Colorectal cancer incidences in Lynch syndrome : a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium. Hereditary Cancer in Clinical Practice, 20(1), Article 36. https://doi.org/10.1186/s13053-022-00241-1

@article{f4e80085ce744f738bcf77c931ddba6e,

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

abstract = "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.",

author = "P. M{\o}ller and T. Sepp{\"a}l{\"a} and Dowty, {J. G.} and S. Haupt and M. Dominguez-Valentin and L. Sunde and I. Bernstein and C. Engel and S. Aretz and M. Nielsen and G. Capella and Evans, {D. G.} and J. Burn and E. Holinski-Feder and L. Bertario and B. Bonanni and A. Lindblom and Z. Levi and F. Macrae and I. Winship and Plazzer, {J. -P.} and R. Sijmons and L. Laghi and Valle, {A. D.} and K. Heinimann and E. Half and F. Lopez-Koestner and K. Alvarez-Valenzuela and Scott, {R. J.} and L. Katz and I. Laish and E. Vainer and Vaccaro, {C. A.} and Carraro, {D. M.} and N. Gluck and N. Abu-Freha and A. Stakelum and R. Kennelly and D. Winter and Rossi, {B. M.} and M. Greenblatt and M. Bohorquez and H. Sheth and Tibiletti, {M. G.} and Lino-Silva, {L. S.} and K. Horisberger and C. Portenkirchner and I. Nascimento and N.T. Rossi and {Apolin{\'a}rio da Silva}, L. and H. Thomas and A. Zar{\'a}nd and Mecklin, {J. -P.} and K. Pylv{\"a}n{\"a}inen and L. Renkonen-Sinisalo and A. Lepisto and P. Peltom{\"a}ki and C. Therkildsen and Lindberg, {L. J.} and O. Thorlacius-Ussing and {Knebel Doeberitz}, M. and M. Loeffler and N. Rahner and V. Steinke-Lange and W. Schmiegel and D. Vangala and C. Perne and R. H{\"u}neburg and {Falc{\'o}n de Vargas}, A. and A. Latchford and Gerdes, {A. -M.} and Backman, {A. -S.} and C. Guill{\'e}n-Ponce and C. Snyder and Lautrup, {C. K.} and D. Amor and E. Palmero and E. Stoffel and F. Duijkers and Hall, {M. J.} and H. Hampel and H. Williams and H. Okkels and J. Lubi{\'n}ski and J. Reece and J. Ngeow and Guillem, {J. G.} and J. Arnold and K. Wadt and K. Monahan and L. Senter and Rasmussen, {L. J.} and {van Hest}, {L. P.} and L. Ricciardiello and Kohonen-Corish, {Maija R. J.} and Ligtenberg, {M. J. L.} and M. Southey and M. Aronson and Zahary, {M. N.} and Samadder, {N. J.} and N. Poplawski and N. Hoogerbrugge and Morrison, {P. J.} and P. James and G. Lee and R. Chen-Shtoyerman and R. Ankathil and R. Pai and R. Ward and S. Parry and T. D{\c e}bniak and T. John and {van Overeem Hansen}, T. and T. Cald{\'e}s and T. Yamaguchi and V. Barca-Tierno and P. Garre and Cavestro, {G. M.} and J. Weitz and S. Redler and R. B{\"u}ttner and V. Heuveline and Hopper, {J. L.} and Win, {A. K.} and N. Lindor and S. Gallinger and {Le Marchand}, L. and Newcomb, {P. A.} and J. Figueiredo and Buchanan, {D. D.} and Thibodeau, {S. N.} and Broeke, {S. W.} and E. Hovig and S. Nakken and M. Pineda and N. Due{\~n}as and J. Brunet and K. Green and F. Lalloo and K. Newton and Crosbie, {E. J.} and M. Mints and D. Tjandra and F. Neffa and P. Esperon and R. Kariv and G. Rosner and Pavicic, {W. H.} and P. Kalfayan and Torrezan, {G. T.} and T. Bassaneze and C. Martin and G. Moslein and A. Ahadova and M. Kloor and Sampson, {J. R.} and Jenkins, {M. A.} and {The European Hereditary Tumour Group (EHTG)} and {International Mismatch Repair Consortium (IMRC)}",

year = "2022",

doi = "10.1186/s13053-022-00241-1",

language = "English",

volume = "20",

journal = "Hereditary Cancer in Clinical Practice",

issn = "1731-2302",

publisher = "BioMed Central",

number = "1",

}

Møller, P, Seppälä, T, Dowty, JG, Haupt, S, Dominguez-Valentin, M, Sunde, L, Bernstein, I, Engel, C, Aretz, S, Nielsen, M, Capella, G, Evans, DG, Burn, J, Holinski-Feder, E, Bertario, L, Bonanni, B, Lindblom, A, Levi, Z, Macrae, F, Winship, I, Plazzer, J-P, Sijmons, R, Laghi, L, Valle, AD, Heinimann, K, Half, E, Lopez-Koestner, F, Alvarez-Valenzuela, K, Scott, RJ, Katz, L, Laish, I, Vainer, E, Vaccaro, CA, Carraro, DM, Gluck, N, Abu-Freha, N, Stakelum, A, Kennelly, R, Winter, D, Rossi, BM, Greenblatt, M, Bohorquez, M, Sheth, H, Tibiletti, MG, Lino-Silva, LS, Horisberger, K, Portenkirchner, C, Nascimento, I, Rossi, NT, Apolinário da Silva, L, Thomas, H, Zaránd, A, Mecklin, J-P, Pylvänäinen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomäki, P, Therkildsen, C, Lindberg, LJ, Thorlacius-Ussing, O, Knebel Doeberitz, M, Loeffler, M, Rahner, N, Steinke-Lange, V, Schmiegel, W, Vangala, D, Perne, C, Hüneburg, R, Falcón de Vargas, A, Latchford, A, Gerdes, A-M, Backman, A-S, Guillén-Ponce, C, Snyder, C, Lautrup, CK, Amor, D, Palmero, E, Stoffel, E, Duijkers, F, Hall, MJ, Hampel, H, Williams, H, Okkels, H, Lubiński, J, Reece, J, Ngeow, J, Guillem, JG, Arnold, J, Wadt, K, Monahan, K, Senter, L, Rasmussen, LJ, van Hest, LP, Ricciardiello, L, Kohonen-Corish, MRJ, Ligtenberg, MJL, Southey, M, Aronson, M, Zahary, MN, Samadder, NJ, Poplawski, N, Hoogerbrugge, N, Morrison, PJ, James, P, Lee, G, Chen-Shtoyerman, R, Ankathil, R, Pai, R, Ward, R, Parry, S, Dębniak, T, John, T, van Overeem Hansen, T, Caldés, T, Yamaguchi, T, Barca-Tierno, V, Garre, P, Cavestro, GM, Weitz, J, Redler, S, Büttner, R, Heuveline, V, Hopper, JL, Win, AK, Lindor, N, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, J, Buchanan, DD, Thibodeau, SN, Broeke, SW, Hovig, E, Nakken, S, Pineda, M, Dueñas, N, Brunet, J, Green, K, Lalloo, F, Newton, K, Crosbie, EJ, Mints, M, Tjandra, D, Neffa, F, Esperon, P, Kariv, R, Rosner, G, Pavicic, WH, Kalfayan, P, Torrezan, GT, Bassaneze, T, Martin, C, Moslein, G, Ahadova, A, Kloor, M, Sampson, JR, Jenkins, MA, The European Hereditary Tumour Group (EHTG) & International Mismatch Repair Consortium (IMRC) 2022, 'Colorectal cancer incidences in Lynch syndrome : a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium', Hereditary Cancer in Clinical Practice, vol. 20, no. 1, 36. https://doi.org/10.1186/s13053-022-00241-1

TY - JOUR

T1 - Colorectal cancer incidences in Lynch syndrome : a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

AU - Møller, P.

AU - Seppälä, T.

AU - Dowty, J. G.

AU - Haupt, S.

AU - Dominguez-Valentin, M.

AU - Sunde, L.

AU - Bernstein, I.

AU - Engel, C.

AU - Aretz, S.

AU - Nielsen, M.

AU - Capella, G.

AU - Evans, D. G.

AU - Burn, J.

AU - Holinski-Feder, E.

AU - Bertario, L.

AU - Bonanni, B.

AU - Lindblom, A.

AU - Levi, Z.

AU - Macrae, F.

AU - Winship, I.

AU - Plazzer, J. -P.

AU - Sijmons, R.

AU - Laghi, L.

AU - Valle, A. D.

AU - Heinimann, K.

AU - Half, E.

AU - Lopez-Koestner, F.

AU - Alvarez-Valenzuela, K.

AU - Scott, R. J.

AU - Katz, L.

AU - Laish, I.

AU - Vainer, E.

AU - Vaccaro, C. A.

AU - Carraro, D. M.

AU - Gluck, N.

AU - Abu-Freha, N.

AU - Stakelum, A.

AU - Kennelly, R.

AU - Winter, D.

AU - Rossi, B. M.

AU - Greenblatt, M.

AU - Bohorquez, M.

AU - Sheth, H.

AU - Tibiletti, M. G.

AU - Lino-Silva, L. S.

AU - Horisberger, K.

AU - Portenkirchner, C.

AU - Nascimento, I.

AU - Rossi, N.T.

AU - Apolinário da Silva, L.

AU - Thomas, H.

AU - Zaránd, A.

AU - Mecklin, J. -P.

AU - Pylvänäinen, K.

AU - Renkonen-Sinisalo, L.

AU - Lepisto, A.

AU - Peltomäki, P.

AU - Therkildsen, C.

AU - Lindberg, L. J.

AU - Thorlacius-Ussing, O.

AU - Knebel Doeberitz, M.

AU - Loeffler, M.

AU - Rahner, N.

AU - Steinke-Lange, V.

AU - Schmiegel, W.

AU - Vangala, D.

AU - Perne, C.

AU - Hüneburg, R.

AU - Falcón de Vargas, A.

AU - Latchford, A.

AU - Gerdes, A. -M.

AU - Backman, A. -S.

AU - Guillén-Ponce, C.

AU - Snyder, C.

AU - Lautrup, C. K.

AU - Amor, D.

AU - Palmero, E.

AU - Stoffel, E.

AU - Duijkers, F.

AU - Hall, M. J.

AU - Hampel, H.

AU - Williams, H.

AU - Okkels, H.

AU - Lubiński, J.

AU - Reece, J.

AU - Ngeow, J.

AU - Guillem, J. G.

AU - Arnold, J.

AU - Wadt, K.

AU - Monahan, K.

AU - Senter, L.

AU - Rasmussen, L. J.

AU - van Hest, L. P.

AU - Ricciardiello, L.

AU - Kohonen-Corish, Maija R. J.

AU - Ligtenberg, M. J. L.

AU - Southey, M.

AU - Aronson, M.

AU - Zahary, M. N.

AU - Samadder, N. J.

AU - Poplawski, N.

AU - Hoogerbrugge, N.

AU - Morrison, P. J.

AU - James, P.

AU - Lee, G.

AU - Chen-Shtoyerman, R.

AU - Ankathil, R.

AU - Pai, R.

AU - Ward, R.

AU - Parry, S.

AU - Dębniak, T.

AU - John, T.

AU - van Overeem Hansen, T.

AU - Caldés, T.

AU - Yamaguchi, T.

AU - Barca-Tierno, V.

AU - Garre, P.

AU - Cavestro, G. M.

AU - Weitz, J.

AU - Redler, S.

AU - Büttner, R.

AU - Heuveline, V.

AU - Hopper, J. L.

AU - Win, A. K.

AU - Lindor, N.

AU - Gallinger, S.

AU - Le Marchand, L.

AU - Newcomb, P. A.

AU - Figueiredo, J.

AU - Buchanan, D. D.

AU - Thibodeau, S. N.

AU - Broeke, S. W.

AU - Hovig, E.

AU - Nakken, S.

AU - Pineda, M.

AU - Dueñas, N.

AU - Brunet, J.

AU - Green, K.

AU - Lalloo, F.

AU - Newton, K.

AU - Crosbie, E. J.

AU - Mints, M.

AU - Tjandra, D.

AU - Neffa, F.

AU - Esperon, P.

AU - Kariv, R.

AU - Rosner, G.

AU - Pavicic, W. H.

AU - Kalfayan, P.

AU - Torrezan, G. T.

AU - Bassaneze, T.

AU - Martin, C.

AU - Moslein, G.

AU - Ahadova, A.

AU - Kloor, M.

AU - Sampson, J. R.

AU - Jenkins, M. A.

AU - The European Hereditary Tumour Group (EHTG), null

AU - International Mismatch Repair Consortium (IMRC), null

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.

UR - https://hdl.handle.net/1959.7/uws:73871

U2 - 10.1186/s13053-022-00241-1

DO - 10.1186/s13053-022-00241-1

M3 - Article

SN - 1731-2302

VL - 20

JO - Hereditary Cancer in Clinical Practice

JF - Hereditary Cancer in Clinical Practice

IS - 1

M1 - 36

ER -

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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