Journal article
Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database
Mev Dominguez-Valentin, Julian R Sampson, Toni T Seppala, Sanne W ten Broeke, John-Paul Plazzer, Sigve Nakken, Christoph Engel, Stefan Aretz, Mark A Jenkins, Lone Sunde, Inge Bernstein, Gabriel Capella, Francesc Balaguer, Huw Thomas, D Gareth Evans, John Burn, Marc Greenblatt, Eivind Hovig, Wouter H de Vos Tot Nederveen Cappel, Rolf H Sijmons Show all
GENETICS IN MEDICINE | NATURE PUBLISHING GROUP | Published : 2020
Abstract
PURPOSE: Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. METHODS: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. RESULTS: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing s..
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Grants
Awarded by Norwegian Cancer Society
Awarded by Manchester National Institute for Health Research (NIHR) Biomedical Research Centre
Awarded by National Cancer Institute of the National Institutes of Health
Awarded by Colorectal Cancer Family Registry (CCFR) center: Australasian Colorectal Cancer Family Registry (National Cancer Institute/National Institutes of Health [NCI/NIH])
Awarded by Colorectal Cancer Family Registry (CCFR) center: Mayo Clinic Cooperative Family Registry for Colon Cancer Studies
Awarded by Colorectal Cancer Family Registry (CCFR) center: Ontario Familial Colorectal Cancer Registry
Awarded by Colorectal Cancer Family Registry (CCFR) center: Seattle Colorectal Cancer Family Registry
Awarded by Colorectal Cancer Family Registry (CCFR) center: University of Hawaii Colorectal Cancer Family Registry
Awarded by Colorectal Cancer Family Registry (CCFR) center: University of Southern California (USC) Consortium Colorectal Cancer Family Registry
Awarded by FEDER funds -a way to build Europe
Awarded by Government of Catalonia
Awarded by Instituto de Salud Carlos III
Funding Acknowledgements
We express our gratitude to Heikki Jarvinen, Anna Lepisto, Beatriz Alcala-Repo, Teresa Ocana, Maria Pellise, Sabela Carballal, Liseth Rivero, Lorena Moreno, Gerhard Jung, Antoni Castells, Joaquin Cubiella, Laura Rivas, Luis Bujanda, Ines Gil, Jesus Banales, Catalina Garau, Rodrigo Jover, Maria Dolores Pico, Xavier Bessa, Cristina Alvarez, Montserrat Andreu, Carmen Poves, Pedro Perez Segura, Lucia Cid, Marta Carrillo, Enrique Quintero, Angeles Pizarro, Marta Garzon, Adolfo Suarez, Inmaculada Salces, Daniel Rodriguez-Alcalde, Judith Balmana, Adria Lopez, Nuria Duenas, Gemma Llort, Carmen Yague, Teresa Ramon i Cajal, David Fisas Masferrer, Alexandra Gisbert Beamud, Consol Lopez San Martin, Maite Herraiz, Pilar Perez, Cristina Carretero, Maite Betes, Marta Ponce, Elena Aguirre, Nora Alfaro, Carlos Sarroca, and Marianne Haeusler for their efforts over the years. We also thank the Finnish Cancer Foundation, Jane and Aatos Erkko Foundation, and the Norwegian Cancer Society, contract 194751-2017 for funding. D.G.E. and E.J.C are supported by the all Manchester National Institute for Health Research (NIHR) Biomedical Research Centre (IS-BRC-1215-20007). Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number UM1CA167551 and through cooperative agreements with the following Colorectal Cancer Family Registry (CCFR) centers: Australasian Colorectal Cancer Family Registry (National Cancer Institute/National Institutes of Health [NCI/NIH] U01 CA074778 and U01/U24 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (NCI/NIH U01/U24 CA074800), Ontario Familial Colorectal Cancer Registry (NCI/NIH U01/U24 CA074783), Seattle Colorectal Cancer Family Registry (NCI/NIH U01/U24 CA074794), University of Hawaii Colorectal Cancer Family Registry (NCI/NIH U01/U24 CA074806 and R01 CA104132 to L.L.M.), University of Southern California (USC) Consortium Colorectal Cancer Family Registry (NCI/NIH U01/U24 CA074799). GC, MP and MN work was funded by the Spanish Ministry of Economy and Competitiveness and cofunded by FEDER funds -a way to build Europe(grant SAF2015-68016-R), CIBERONC and the Government of Catalonia (grants 2017SGR1282 and PERIS SLT002/16/0037). The German Consortium for Familial Intestinal Cancer has been supported by grants from the German Cancer Aid. Data collection in Bonn was facilitated by the Center for Hereditary Tumor Syndromes, University of Bonn. F.B. is supported by grants from the Instituto de Salud Carlos III (PI13/00719; PI16/00766) and from the Asociacion Espanola de Gastroenterologia (AEG). Data collection from Wales, UK was supported by the Wales Gene Park. This work was cofunded by the European Regional Development Fund (ERDF).