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Each inherited loss-of-function variant produces one of four Lynch cancer syndromes with distinct penetrance and expressivity. The document frames tumor development as a linear progression plus a dynamic balance between MSI-generated abnormal cells and host adaptive immune clearance, explaining surveillance effects and supporting roles for aspirin prevention and immunotherapy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dominantly-inherited-micro-satellite-instable-cancer-the-four-lynch-syndromes-an-ehtg-plsd-position-statement/379328/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/dominantly-inherited-micro-satellite-instable-cancer-the-four-lynch-syndromes-an-ehtg-plsd-position-statement/379328.png","ImageObject",300,407,{"name":92,"@type":93},"supergirl","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which genes cause dominantly inherited MSI cancers in the four Lynch syndromes?","Question",{"text":112,"@type":113},"Pathogenic variants in one of four mismatch repair (MMR) genes—MSH2, MLH1, MSH6, and PMS2—cause dominantly inherited MSI cancers that correspond to the four Lynch syndromes.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the document describe the process from MSI to cancer development?",{"text":117,"@type":113},"It describes carcinogenesis as a progression from increased cellular division to localized cancer to metastasis, alongside a dynamic balance between MSI producing abnormal cells and the host’s adaptive immune system removing them.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic and preventive approaches are highlighted for Lynch syndromes?",{"text":121,"@type":113},"The document highlights aspirin reducing incidence of colorectal and other cancers in Lynch syndromes and immunotherapy increasing the host immune system’s capacity to destroy MSI cancers, alongside colonoscopy surveillance and personalized precision medicine strategies.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},379328,1790421887,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},962088121634,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Møller et al.  \nHereditary Cancer in Clinical Practice (2023) 21:19 [https://doi.org/10.1186/s13053-023-00263-3](https://doi.org/10.1186/s13053-023-00263-3)  \nHereditary Cancer in Clinical Practice  \n REVIEW Open Access  \nDominantly inherited micro-satellite instable   cancer – the four Lynch syndromes-an EHTG, PLSD position statement  \nPal Møller1*, ToniT. Seppälä2,3,4, Aysel Ahadova5,6,7, Emma J. Crosbie8,9, Elke Holinski‑Feder10,11, Rodney Scott12, Saskia Haupt13,14, Gabriela Möslein15, Ingrid Winship16,17, Sanne W. Bajwa‑ten Broeke18, Kelly E. Kohut 19, Neil Ryan20,21, Peter Bauerfeind22, Laura E. Thomas23, D. Gareth Evans24, Stefan Aretz25,26, Rolf H. Sijmons27, Elizabeth Half28, Karl Heinimann29, Karoline Horisberger30, Kevin Monahan31, Christoph Engel32,  \nGiulia Martina Cavestro33, Robert Fruscio34, Naim Abu‑Freha35, Levi Zohar36, Luigi Laghi37,38, Lucio Bertario39, Bernardo Bonanni40, Maria Grazia Tibiletti41, Leonardo S. Lino‑Silva42, Carlos Vaccaro43, Adriana Della Valle44, Benedito Mauro Rossi45, Leandro Apolinário da Silva46, Ivana Lucia de Oliveira Nascimento47,  \nNorma Teresa Rossi48, Tadeusz Dębniak49, Jukka‑Pekka Mecklin50,51, Inge Bernstein52,53,54, Annika Lindblom55,56, Lone Sunde57,58, Sigve Nakken1,59,60, Vincent Heuveline13,14, John Burn61, Eivind Hovig1,59, Matthias Kloor5,6,7, Julian R. Sampson62, Mev Dominguez‑Valentin1 and On behalf of the Prospective Lynch Syndrome Database ([www.plsd.eu](www.plsd.eu)) and The European Hereditary Tumour Group ([www.ehtg.org](www.ehtg.org))  \nAbstract  \nThe recognition of dominantly inherited micro‑satellite instable (MSI) cancers caused by pathogenic variants in oneof the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcino‑ genesis. 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 “ora 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 metas‑ tasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic pro‑ cesses: 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 cancersin LS. Immunotherapy increases the host immune system’s capability to destroy MSI cancers. Colonoscopy surveil‑ lance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.  \n*Correspondence: Pal Møller [moller.pal@gmail.com](moller.pal@gmail.com)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.","cbCaikWbYYNWmzHP","https://ap.wps.com/l/cbCaikWbYYNWmzHP","pdf",1641692,12,"English","# Abstract\n## Introduction\n## Clinical management background and guideline updates","[{\"question\":\"Which genes cause dominantly inherited MSI cancers in the four Lynch syndromes?\",\"answer\":\"Pathogenic variants in one of four mismatch repair (MMR) genes—MSH2, MLH1, MSH6, and PMS2—cause dominantly inherited MSI cancers that correspond to the four Lynch syndromes.\"},{\"question\":\"How does the document describe the process from MSI to cancer development?\",\"answer\":\"It describes carcinogenesis as a progression from increased cellular division to localized cancer to metastasis, alongside a dynamic balance between MSI producing abnormal cells and the host’s adaptive immune system removing them.\"},{\"question\":\"What therapeutic and preventive approaches are highlighted for Lynch syndromes?\",\"answer\":\"The document highlights aspirin reducing incidence of colorectal and other cancers in Lynch syndromes and immunotherapy increasing the host immune system’s capacity to destroy MSI cancers, alongside colonoscopy surveillance and personalized precision medicine strategies.\"}]","Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement | PDF",1790235130]