Journal article

Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

Mark A Jenkins

LANCET ONCOLOGY | ELSEVIER SCIENCE INC | Published : 2021

Abstract

BACKGROUND: Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence. METHODS: In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. F..

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Grants

Awarded by National Health and Medical Research Council (NHMRC), Australia


Awarded by National Institutes of Health (NIH)


Awarded by German Cancer Aid


Awarded by NHMRC


Awarded by NIH/NCI


Awarded by NIH


Awarded by University Sains Malaysia Research University grant


Awarded by Dutch Cancer Society


Awarded by Fondo Investigacion Sanitaria Instituto Salud Carlos III


Awarded by National Institute for Health Research Manchester Biomedical Research Centre Grant


Awarded by Canadian Institutes of Health Research Foundation


Awarded by Cancer Council NSW


Awarded by Southampton Centre


Awarded by German Research Foundation Deutsche Forschungsgemeinschaft


Awarded by Hector-Foundation


Awarded by FINEP-CT-INFRA


Awarded by PRONON/MS


Awarded by Fondazione AIRC per la Ricerca Sul Cancro investigator grant


Awarded by Danish Cancer Society


Awarded by Norwegian Cancer Society


Awarded by National Medical Research Council Singapore Clinical Scientist Award


Funding Acknowledgements

This work was supported by project grant 1063840 from the National Health and Medical Research Council (NHMRC), Australia. The Colon Cancer Family Registry is supported, in part, by funding from the National Cancer Institute (NCI), National Institutes of Health (NIH) award U01 CA167551. Additional support for case ascertainment was provided, in part, from the Surveillance, Epidemiology, and End Results Program, US state cancer registries in Arizona, Colorado, Minnesota, North Carolina, and New Hampshire, the Victoria Cancer Registry (Australia), and the Ontario Cancer Registry (Canada). The German Consortium for Familial Intestinal Cancer is supported by grants from the German Cancer Aid. The Inherited Cancer Connect Partnership is funded by the Cancer Council New South Wales Strategic Research Partnership scheme. Data collection for Wales was supported by Wales Gene Park, funded by Health and Care Research Wales. Data collection for the Hereditary Cancer Center at Creighton University was supported by revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services. This work is also funded by the following grants: NHMRC Career Development Fellowship 1141746 (AKW), Early Career Fellowship 1120081 (JCR), Career Development Fellowship 1125268 (DDB), Senior Research Fellowship 1061779 and Investigator Grant 1177524 (ABS), Senior Research Fellowship 1117611 (MAJ), Senior Principal Research Fellowship 1137349 (JLH), NIH/NCI R01 CA132829 (SS); NIH U01/U24 CA074800 (RKP), NIH/NCI RC4CA153828 (JWe), University Sains Malaysia Research University grant 1001/CIPPT/813005 (RAn); German Cancer Aid Grant No.190370 (SAr), the Bengt Ihre Research Foundation and the Swedish Society of Medicine (AB), Dutch Cancer Society Grant UL-2012-5515 (SWB-tB); Fondo Investigacion Sanitaria PI 16/01292 Instituto Salud Carlos III (TC), the Genesis Foundation, Montevideo, Uruguay (ADValle), the National Institute for Health Research Manchester Biomedical Research Centre Grant (reference number 1215-200074; DGE), Canadian Institutes of Health Research Foundation Grant 148390 (WF), Fondo Investigacion Sanitaria PI 19/1366 Instituto Salud Carlos III (PG), Cancer Council NSW RG 19-01 (MRJK-C); Cancer Research UK, the Southampton Centre C328/A25139 (AML), the German Research Foundation Deutsche Forschungsgemeinschaft, SFB TR57, SPP1937, and the Hector-Foundation M89 (JNa), the South African Medical Research Council (RR), Nordea-fonden, the Novo Nordisk Foundation, the Olav Thon Foundation, and Sven Wewers fond (LJR), FINEP-CT-INFRA (02/2010) and PRONON/MS (25000.056766/2015-64; RMR), Fondazione AIRC per la Ricerca Sul Cancro investigator grant 21723 (LR); German Cancer Aid (WS), the Danish Cancer Society A-14570 (CT), Dr. Norman & Melinda Payson Professorship in Medical Oncology (JNW), the Norwegian Cancer Society Contract 194751-2017 (MD-V), the Jane and Aatos Erkko Foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Sigrid Juselius Foundation, the Instrumentarium Science Foundation, and the iCAN Flagship of the Academy of Finland and Cancer Foundation Finland (TTS and JM), and the National Medical Research Council Singapore Clinical Scientist Award NMRC/CSA-INV/0017/2017 (JNg). The content of this Article does not necessarily reflect the views or policies of any of the sponsors or collaborating centres in the IMRC, nor does mention of trade names, commercial products, or organisations imply endorsement by the IMRC.r We thank all study participants and staff from all collaborative centres of the IMRC for their contributions to this work, including, but not limited to, Donna Job (Newcastle University, Newcastle, UK) and Chris Michael-Lovatt (Peter MacCallum Cancer Centre, Melbourne, VIC, Australia).