Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement
Abstract 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 ge...
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
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| Series: | Hereditary Cancer in Clinical Practice |
| Online Access: | https://doi.org/10.1186/s13053-023-00263-3 |
| _version_ | 1797451282491899904 |
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| author | Pal Møller Toni T. Seppälä Aysel Ahadova Emma J. Crosbie Elke Holinski-Feder Rodney Scott Saskia Haupt Gabriela Möslein Ingrid Winship Sanne W. Bajwa-ten Broeke Kelly E. Kohut Neil Ryan Peter Bauerfeind Laura E. Thomas D. Gareth Evans Stefan Aretz Rolf H. Sijmons Elizabeth Half Karl Heinimann Karoline Horisberger Kevin Monahan Christoph Engel Giulia Martina Cavestro Robert Fruscio Naim Abu-Freha Levi Zohar Luigi Laghi Lucio Bertario Bernardo Bonanni Maria Grazia Tibiletti Leonardo S. Lino-Silva Carlos Vaccaro Adriana Della Valle Benedito Mauro Rossi Leandro Apolinário da Silva Ivana Lucia de Oliveira Nascimento Norma Teresa Rossi Tadeusz Dębniak Jukka-Pekka Mecklin Inge Bernstein Annika Lindblom Lone Sunde Sigve Nakken Vincent Heuveline John Burn Eivind Hovig Matthias Kloor Julian R. Sampson Mev Dominguez-Valentin On behalf of the Prospective Lynch Syndrome Database (www.plsd.eu) and The European Hereditary Tumour Group (www.ehtg.org) |
| author_facet | Pal Møller Toni T. Seppälä Aysel Ahadova Emma J. Crosbie Elke Holinski-Feder Rodney Scott Saskia Haupt Gabriela Möslein Ingrid Winship Sanne W. Bajwa-ten Broeke Kelly E. Kohut Neil Ryan Peter Bauerfeind Laura E. Thomas D. Gareth Evans Stefan Aretz Rolf H. Sijmons Elizabeth Half Karl Heinimann Karoline Horisberger Kevin Monahan Christoph Engel Giulia Martina Cavestro Robert Fruscio Naim Abu-Freha Levi Zohar Luigi Laghi Lucio Bertario Bernardo Bonanni Maria Grazia Tibiletti Leonardo S. Lino-Silva Carlos Vaccaro Adriana Della Valle Benedito Mauro Rossi Leandro Apolinário da Silva Ivana Lucia de Oliveira Nascimento Norma Teresa Rossi Tadeusz Dębniak Jukka-Pekka Mecklin Inge Bernstein Annika Lindblom Lone Sunde Sigve Nakken Vincent Heuveline John Burn Eivind Hovig Matthias Kloor Julian R. Sampson Mev Dominguez-Valentin On behalf of the Prospective Lynch Syndrome Database (www.plsd.eu) and The European Hereditary Tumour Group (www.ehtg.org) |
| author_sort | Pal Møller |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T14:52:27Z |
| format | Article |
| id | doaj.art-952d37829e8040c192582717c1ee47f5 |
| institution | Directory Open Access Journal |
| issn | 1897-4287 |
| language | English |
| last_indexed | 2024-03-09T14:52:27Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditary Cancer in Clinical Practice |
| spelling | doaj.art-952d37829e8040c192582717c1ee47f52023-11-26T14:23:33ZengBMCHereditary Cancer in Clinical Practice1897-42872023-10-0121111210.1186/s13053-023-00263-3Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statementPal Møller0Toni T. Seppälä1Aysel Ahadova2Emma J. Crosbie3Elke Holinski-Feder4Rodney Scott5Saskia Haupt6Gabriela Möslein7Ingrid Winship8Sanne W. Bajwa-ten Broeke9Kelly E. Kohut10Neil Ryan11Peter Bauerfeind12Laura E. Thomas13D. Gareth Evans14Stefan Aretz15Rolf H. Sijmons16Elizabeth Half17Karl Heinimann18Karoline Horisberger19Kevin Monahan20Christoph Engel21Giulia Martina Cavestro22Robert Fruscio23Naim Abu-Freha24Levi Zohar25Luigi Laghi26Lucio Bertario27Bernardo Bonanni28Maria Grazia Tibiletti29Leonardo S. Lino-Silva30Carlos Vaccaro31Adriana Della Valle32Benedito Mauro Rossi33Leandro Apolinário da Silva34Ivana Lucia de Oliveira Nascimento35Norma Teresa Rossi36Tadeusz Dębniak37Jukka-Pekka Mecklin38Inge Bernstein39Annika Lindblom40Lone Sunde41Sigve Nakken42Vincent Heuveline43John Burn44Eivind Hovig45Matthias Kloor46Julian R. Sampson47Mev Dominguez-Valentin48On behalf of the Prospective Lynch Syndrome Database (www.plsd.eu) and The European Hereditary Tumour Group (www.ehtg.org)Department of Tumor Biology, Institute of Cancer Research, Oslo University HospitalFaculty of Medicine and Health Technology, Cancer Centre, Tampere University and Tays, Tampere University HospitalDepartment of Applied Tumour Biology, Institute of Pathology, Heidelberg University HospitalGynaecological Oncology Research Group, Manchester University NHS Foundation TrustMedizinische Klinik Und Poliklinik IV, Klinikum Der Universität MünchenHunter Medical Research Institute, University of NewcastleEngineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg UniversitySurgical Center for Hereditary Tumors, Academic Hospital UniversityGenomic Medicine, The Royal Melbourne HospitalDepartment of Genetics, University of Groningen, University Medical Center GroningenCentre for Psychosocial Research in Cancer, Health Sciences, University of SouthamptonMedical School, University of EdinburghHirslanden clinicInstitute of Life Science, Swansea UniversityManchester Centre for Genomic Medicine, Division of Evolution Infection and Genomic Sciences, University of ManchesterInstitute of Human Genetics, Medical Faculty, University of BonnDepartment of Genetics, University of Groningen, University Medical Center GroningenGastrointestinal Cancer Prevention Unit, Gastroenterology Department, Rambam Health Care CampusMedical Genetics, Institute for Medical Genetics and Pathology, University Hospital BaselDepartment of General, Visceral and Transplatation Surgery, University Hospital of MainzLynch Syndrome & Family Cancer Clinic, Centre for Familial Intestinal Cancer, St Mark’s HospitalInstitute for Medical Informatics, Statistics and Epidemiology, University of LeipzigGastroenterology and Gastrointestinal Endoscopy Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele UniversityClinic of Obstetrics and Gynecology, Department of Medicine and Surgery, University of Milan-Bicocca, Fondazione IRCCS San GerardoSoroka University Medical Center, Ben-Gurion University of the NegevService High Risk GI Cancer Gastroenterology, Department Rabin Medical CenterLaboratory of Molecular Gastroenterology, IRCCS Humanitas Research HospitalDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology, Fondazione IRCCS Instituto Nazionale dei Tumori, IRCCSDivision of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCSOspedale di Circolo ASST Settelaghi, Università dell’InsubriaSurgical Pathology, Instituto Nacional de CancerologiaInstituo Medicina Translacional e Ingenieria Biomedica - Hospital Italiano Bs As. - CONICETHospital Central de las Fuerzas Armadas, Grupo Colaborativo Uruguayo, Investigación de Afecciones Oncológicas Hereditarias (GCU)Hospital Sírio-LibanêsHospital Universitário Oswaldo Cruz/Universidade de PernambucoInstituto de Ciência da Saúde da UFBA/NOB-Grupo OncoclinicasFundación para el Progreso de la Medicina y Sanatorio AllendeDepartment of Genetics and Pathology, Pomeranian Medical UniversityFaculty of Sport and Health Sciences, University of JyväskyläDepartment of Surgical Gastroenterology, Aalborg University Hospital, Aalborg UniversityDepartment of Molecular Medicine and Surgery, Karolinska InstitutetDepartment of Clinical Genetics, Aalborg University HospitalDepartment of Tumor Biology, Institute of Cancer Research, Oslo University HospitalEngineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg UniversityFaculty of Medical Sciences, Newcastle UniversityDepartment of Tumor Biology, Institute of Cancer Research, Oslo University HospitalDepartment of Applied Tumour Biology, Institute of Pathology, Heidelberg University HospitalInstitute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of MedicineDepartment of Tumor Biology, Institute of Cancer Research, Oslo University HospitalAbstract 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.https://doi.org/10.1186/s13053-023-00263-3 |
| spellingShingle | Pal Møller Toni T. Seppälä Aysel Ahadova Emma J. Crosbie Elke Holinski-Feder Rodney Scott Saskia Haupt Gabriela Möslein Ingrid Winship Sanne W. Bajwa-ten Broeke Kelly E. Kohut Neil Ryan Peter Bauerfeind Laura E. Thomas D. Gareth Evans Stefan Aretz Rolf H. Sijmons Elizabeth Half Karl Heinimann Karoline Horisberger Kevin Monahan Christoph Engel Giulia Martina Cavestro Robert Fruscio Naim Abu-Freha Levi Zohar Luigi Laghi Lucio Bertario Bernardo Bonanni Maria Grazia Tibiletti Leonardo S. Lino-Silva Carlos Vaccaro Adriana Della Valle Benedito Mauro Rossi Leandro Apolinário da Silva Ivana Lucia de Oliveira Nascimento Norma Teresa Rossi Tadeusz Dębniak Jukka-Pekka Mecklin Inge Bernstein Annika Lindblom Lone Sunde Sigve Nakken Vincent Heuveline John Burn Eivind Hovig Matthias Kloor Julian R. Sampson Mev Dominguez-Valentin On behalf of the Prospective Lynch Syndrome Database (www.plsd.eu) and The European Hereditary Tumour Group (www.ehtg.org) Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement Hereditary Cancer in Clinical Practice |
| title | Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement |
| title_full | Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement |
| title_fullStr | Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement |
| title_full_unstemmed | Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement |
| title_short | Dominantly inherited micro-satellite instable cancer – the four Lynch syndromes - an EHTG, PLSD position statement |
| title_sort | dominantly inherited micro satellite instable cancer the four lynch syndromes an ehtg plsd position statement |
| url | https://doi.org/10.1186/s13053-023-00263-3 |
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