Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database
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The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. Here we use the most recent PLSD cohort that is larger and has wider geographical representation than previous versions, allowing us to present mortality as an outcome, and median ages at cancer diagnoses for the first time.
Methods
The PLSD is a prospective observational study without a control group that was designed in 2012 and updated up to October 2022. Data for 8500 carriers of path_MMR variants from 25 countries were included, providing 71,713 years of follow up. Cumulative cancer incidences at 65 years of age were combined with 10-year crude survival following cancer, to derive estimates of mortality up to 75 years of age by organ, gene, and gender.
Findings
Gynaecological cancers were more frequent than colorectal cancers in path_MSH2, path_MSH6 and path_PMS2 carriers [cumulative incidence: 53.3%, 49.6% and 23.3% at 75 years, respectively]. Endometrial, colon and ovarian cancer had low mortality [8%, 13% and 15%, respectively] and prostate cancers were frequent in male path_MSH2 carriers [cumulative incidence: 39.7% at 75 years]. Pancreatic, brain, biliary tract and ureter and kidney and urinary bladder cancers were associated with high mortality [83%, 66%, 58%, 27%, and 29%, respectively]. Among path_MMR carriers undergoing colonoscopy surveillance, particularly path_MSH2 carriers, more deaths followed non-colorectal Lynch syndrome cancers than colorectal cancers.
Interpretation
In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome.
Funding
We acknowledge funding from the Norwegian Cancer Society, contract 194751-2017.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 101909 |
| Tidsskrift | EClinicalMedicine |
| Vol/bind | 58 |
| Antal sider | 12 |
| ISSN | 2589-5370 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
JRS acknowledges the support from the Wales Gene Park (funded by Welsh Government via Health and Care Wales ). Finnish contribution was supported by grants and research funding from Sigrid Jusélius Foundation , Emil Aaltonen Foundation , Jane and Aatos Erkko Foundation , Relander Foundation , and the iCAN precision medicine flagship of the Finnish Academy. JPP has received funding support from the RMH Allan Watt and Chris Geyer Oncology Fellowship . We acknowledge funding from the Norwegian Cancer Society , contract 194751-2017 . The Colon CFR is supported in part by the National Cancer Institute of the National Institutes of Health under Award Number UM1CA167551 . The Finnish contribution: Cancer Foundation Finland , Jane and Aatos Erkko Foundation , Emil Aaltonen Foundation , Sigrid Jusélius Foundation , Relander Foundation , iCAN Flagship of the Academy of Finland . D.G.E. is supported by the Manchester National Institute for Health Research (NIHR) Biomedical Research Centre ( IS-BRC-1215-20007 ). ECJ is supported by Manchester National Institute for Health and Care Research (NIHR) Biomedical Research Centre and NIHR Advanced Fellowship. The contribution from Wales was supported by the Wales Gene Park award from Health and Care Research Wales . The German Consortium for Familial Intestinal Cancer was supported by grants from the German Cancer Aid . Work by G.C., J.B., and M.P. was funded by the Spanish Ministry of Science and Innovation and cofounded by FEDER M.D. Catalonia (grants 2017SGR1282 ). GC was supported by the Spanish Ministry of Economy and Competitiveness and the Spanish Ministry of Science and Innovation , co-funded by FEDER funds ( PID2019-111254RB-I00 ; IMPaCT Genomica IMP/0009), CIBERONC ( CB16/12/00234 )). GC thank the CERCA Programme for institutional support. FM is supported by Synergy Grant – 2021/GNT2010268 , Targeted Research - 2021/GNT2014703 , Cancer Australia – Capp3, Victorian Cancer Agency – Capp3, 2016.339. DV is supported by the German Cancer Aid . SWtB is supported by Dutch Cancer Society grant for research . MVKD is member of the advisory board of PAICON GmbH ( www.paicon.com ). MG is member of the Hereditary Colon Cancer VCEP Chair, Sequence Variant Interpretation Working Group. J.R.-B. is supported by Instituto de Salud Carlos III , Ministerio de Ciencia e Innovación - Juan Rodés contract (JR21/00019) and a 2020 TTD Research Grant from the Spanish Cooperative Group for the Treatment of Digestive Tumors. HS contributed with support from the Gujarat State Biotechnology Mission (GSBTM/JD (R&D)/604/2018-2019/7). D.M.C and G.T.T were funded by The São Paulo Research Foundation ( FAPESP grant number 2014/50943-1 ) and National Council for Scientific and Technological Development ( CNPq grant number 465682/2014-6 ). KM was funded from the 40tude charity for the Lynch Cancer (LynC) Prevention Study, UK. The work by M.N. was funded by the Dutch Digestive Foundation (FP16-06). GC reports fees from the Spanish Ministry of Economy and Competitiveness and the Spanish Ministry of Science and Innovation , co-funded by FEDER funds—a way to build Europe—(PID2019-111254RB-I00; IMPaCT Genomica IMP/0009), CIBERONC ( CB16/12/00234 ) and The Government of Catalonia . LL reports a relationship with Humanitas Clinical and Research Center , University of Parma .
Publisher Copyright:
© 2023 The Author(s)
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