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

IF 2 4区医学 Q3 ONCOLOGY

Hereditary Cancer in Clinical Practice Pub Date : 2022-10-01 DOI:10.1186/s13053-022-00241-1

Pål Møller, Toni Seppälä, James G Dowty, Saskia Haupt, Mev Dominguez-Valentin, Lone Sunde, Inge Bernstein, Christoph Engel, Stefan Aretz, Maartje Nielsen, Gabriel Capella, Dafydd Gareth Evans, John Burn, Elke Holinski-Feder, Lucio Bertario, Bernardo Bonanni, Annika Lindblom, Zohar Levi, Finlay Macrae, Ingrid Winship, John-Paul Plazzer, Rolf Sijmons, Luigi Laghi, Adriana Della Valle, Karl Heinimann, Elizabeth Half, Francisco Lopez-Koestner, Karin Alvarez-Valenzuela, Rodney J Scott, Lior Katz, Ido Laish, Elez Vainer, Carlos Alberto Vaccaro, Dirce Maria Carraro, Nathan Gluck, Naim Abu-Freha, Aine Stakelum, Rory Kennelly, Des Winter, Benedito Mauro Rossi, Marc Greenblatt, Mabel Bohorquez, Harsh Sheth, Maria Grazia Tibiletti, Leonardo S Lino-Silva, Karoline Horisberger, Carmen Portenkirchner, Ivana Nascimento, Norma Teresa Rossi, Leandro Apolinário da Silva, Huw Thomas, Attila Zaránd, Jukka-Pekka Mecklin, Kirsi Pylvänäinen, Laura Renkonen-Sinisalo, Anna Lepisto, Päivi Peltomäki, Christina Therkildsen, Lars Joachim Lindberg, Ole Thorlacius-Ussing, Magnus von Knebel Doeberitz, Markus Loeffler, Nils Rahner, Verena Steinke-Lange, Wolff Schmiegel, Deepak Vangala, Claudia Perne, Robert Hüneburg, Aída Falcón de Vargas, Andrew Latchford, Anne-Marie Gerdes, Ann-Sofie Backman, Carmen Guillén-Ponce, Carrie Snyder, Charlotte K Lautrup, David Amor, Edenir Palmero, Elena Stoffel, Floor Duijkers, Michael J Hall, Heather Hampel, Heinric Williams, Henrik Okkels, Jan Lubiński, Jeanette Reece, Joanne Ngeow, Jose G Guillem, Julie Arnold, Karin Wadt, Kevin Monahan, Leigha Senter, Lene J Rasmussen, Liselotte P van Hest, Luigi Ricciardiello, Maija R J Kohonen-Corish, Marjolijn J L Ligtenberg, Melissa Southey, Melyssa Aronson, Mohd N Zahary, N Jewel Samadder, Nicola Poplawski, Nicoline Hoogerbrugge, Patrick J Morrison, Paul James, Grant Lee, Rakefet Chen-Shtoyerman, Ravindran Ankathil, Rish Pai, Robyn Ward, Susan Parry, Tadeusz Dębniak, Thomas John, Thomas van Overeem Hansen, Trinidad Caldés, Tatsuro Yamaguchi, Verónica Barca-Tierno, Pilar Garre, Giulia Martina Cavestro, Jürgen Weitz, Silke Redler, Reinhard Büttner, Vincent Heuveline, John L Hopper, Aung Ko Win, Noralane Lindor, Steven Gallinger, Loïc Le Marchand, Polly A Newcomb, Jane Figueiredo, Daniel D Buchanan, Stephen N Thibodeau, Sanne W Ten Broeke, Eivind Hovig, Sigve Nakken, Marta Pineda, Nuria Dueñas, Joan Brunet, Kate Green, Fiona Lalloo, Katie Newton, Emma J Crosbie, Miriam Mints, Douglas Tjandra, Florencia Neffa, Patricia Esperon, Revital Kariv, Guy Rosner, Walter Hernán Pavicic, Pablo Kalfayan, Giovana Tardin Torrezan, Thiago Bassaneze, Claudia Martin, Gabriela Moslein, Aysel Ahadova, Matthias Kloor, Julian R Sampson, Mark A Jenkins

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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. 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引用次数: 0

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.

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林奇综合征的结直肠癌发病率：前瞻性林奇综合征数据库与国际错配修复联盟的结果比较。

目的：比较 PLSD 和 IMRC 队列中 MMR 基因致病性变异携带者的结直肠癌（CRC）发病率，其中只有前者对所有参与者进行了强制性结肠镜监测：在干预组中计算了癌症发病率，该干预组由错配修复基因（path_MMR）致病性或可能致病性变异的确诊携带者组成，由前瞻性林奇综合征数据库（PLSD）进行前瞻性跟踪。所有患者都接受了结肠镜检查，并在发现息肉时进行了息肉切除术。与国际错配修复联盟（IMRC）报告的回顾性队列进行了比较。该队列由林奇综合征疑似患者的一级或二级亲属中经证实和推断的路径_MMR携带者组成：结果：在 PLSD 中，8153 名受试者接受了共计 67604 年的结肠镜随访监测，其中 578 名携带者确诊为 CRC。路径_MLH1携带者在70岁时的平均累积癌症发病率为：男性52%，女性41%；路径_MSH2为50%，女性39%；路径_MSH6为13%，男性17%；路径_PMS2为11%，女性8%。相比之下，在IMRC队列中，相应的累积发病率分别为40%和27%；34%和23%；16%和8%以及7%和6%。仅比较这两个系列中的欧洲带原者，也得出了类似的结果。PLSD 系列中的数字无法单独比较其他大洲携带者的情况。在所有回顾性研究组中，25年的累积发病率均小于1%：接受结肠镜监测和息肉切除术的路径_MLH1和路径_MSH2携带者的前瞻性观察CRC发病率（PLSD）高于回顾性系列（IMRC），而路径_MSH6携带者的发病率并未降低。这些结果与预期相反。接受结肠镜检查的 path_PMS2 携带者 50 岁前的 CRC 点发病率有所降低，但并不明显。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditary Cancer in Clinical Practice 医学-肿瘤学

CiteScore

3.10

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Hereditary Cancer in Clinical Practice is an open access journal that publishes articles of interest for the cancer genetics community and serves as a discussion forum for the development appropriate healthcare strategies. Cancer genetics encompasses a wide variety of disciplines and knowledge in the field is rapidly growing, especially as the amount of information linking genetic differences to inherited cancer predispositions continues expanding. With the increased knowledge of genetic variability and how this relates to cancer risk there is a growing demand not only to disseminate this information into clinical practice but also to enable competent debate concerning how such information is managed and what it implies for patient care. Topics covered by the journal include but are not limited to: Original research articles on any aspect of inherited predispositions to cancer. Reviews of inherited cancer predispositions. Application of molecular and cytogenetic analysis to clinical decision making. Clinical aspects of the management of hereditary cancers. Genetic counselling issues associated with cancer genetics. The role of registries in improving health care of patients with an inherited predisposition to cancer.