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Lookup NU author(s): Professor Sir John BurnORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, BioMed Central.The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an “average sex “or a pathogenic variant in an “average Lynch syndrome gene” and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host’s adaptive immune system’s ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system’s capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.
Author(s): Moller P, Seppala TT, Ahadova A, Crosbie EJ, Holinski-Feder E, Scott R, Haupt S, Moslein G, Winship I, Broeke SWB-T, Kohut KE, Ryan N, Bauerfeind P, Thomas LE, Evans DG, Aretz S, Sijmons RH, Half E, Heinimann K, Horisberger K, Monahan K, Engel C, Cavestro GM, Fruscio R, Abu-Freha N, Zohar L, Laghi L, Bertario L, Bonanni B, Tibiletti MG, Lino-Silva LS, Vaccaro C, Valle AD, Rossi BM, da Silva LA, de Oliveira Nascimento IL, Rossi NT, Debniak T, Mecklin J-P, Bernstein I, Lindblom A, Sunde L, Nakken S, Heuveline V, Burn J, Hovig E, Kloor M, Sampson JR, Dominguez-Valentin M
Publication type: Review
Publication status: Published
Journal: Hereditary Cancer in Clinical Practice
Year: 2023
Volume: 21
Issue: 1
Online publication date: 11/10/2023
Acceptance date: 29/09/2023
ISSN (print): 1731-2302
ISSN (electronic): 1897-4287
Publisher: BioMed Central Ltd
URL: https://doi.org/10.1186/s13053-023-00263-3
DOI: 10.1186/s13053-023-00263-3
