Objectif Recent evidence demonstrates that cancer is overtaking cardiovascular disease as the number one cause of mortality in Europe. This is largely due to the lack of preventative measures for common (e.g. breast) or highly fatal (e.g. ovarian) human cancers. Most cancers are multifactorial in origin. The core hypothesis of this research programme is that the extremely high risk of BRCA1/2 germline mutation carriers to develop breast and ovarian cancer is a net consequence of cell-autonomous (direct effect of BRCA mutation in cells at risk) and cell non-autonomous (produced in distant organs and affecting organs at risk) factors which both trigger epigenetic, cancer-initiating effects. The project’s aims are centered around the principles of systems medicine and built on a large cohort of BRCA mutation carriers and controls who will be offered newly established cancer screening programmes. We will uncover how ‘cell non-autonomous’ factors work, provide detail on the epigenetic changes in at-risk tissues and investigate whether these changes are mechanistically linked to cancer, study whether we can neutralise this process and measure success in the organs at risk, and ideally in easy to access samples such as blood, buccal and cervical cells.In my Department for Women’s Cancer we have assembled a powerful interdisciplinary team including computational biologists, functionalists, immunologists and clinician scientists linked to leading patient advocacy groups which is extremely well placed to lead this pioneering project to develop the fundamental understanding of cancer development in women with BRCA mutations. To reset the epigenome, re-establishing normal cell identity and consequently reducing cancer risk without the need for surgery and being able to monitor the efficacy using multicellular epigenetic outcome predictors will be a major scientific and medical breakthrough and possibly applicable to other chronic diseases. Champ scientifique medical and health sciencesclinical medicinesurgerynatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicinecardiologycardiovascular diseasesmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsepigenetics Mots‑clés Cancer and its biological basis Women's cancers breast cancer ovarian cancer BRCA1 2 mutation cell non-autonomous hormones prevention early diagnosis surrogate markers Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2016-ADG - ERC Advanced Grant Appel à propositions ERC-2016-ADG Voir d’autres projets de cet appel Régime de financement ERC-ADG - Advanced Grant Institution d’accueil UNIVERSITAET INNSBRUCK Contribution nette de l'UE € 1 115 793,00 Adresse INNRAIN 52 6020 Innsbruck Autriche Voir sur la carte Région Westösterreich Tirol Innsbruck Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 115 793,00 Bénéficiaires (5) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire UNIVERSITAET INNSBRUCK Autriche Contribution nette de l'UE € 1 115 793,00 Adresse INNRAIN 52 6020 Innsbruck Voir sur la carte Région Westösterreich Tirol Innsbruck Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 115 793,00 UNIVERSITY COLLEGE LONDON HOSPITALSNHS FOUNDATION TRUST Royaume-Uni Contribution nette de l'UE € 233 251,25 Adresse EUSTON ROAD 250 NW1 2PG London Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 233 251,25 UNIVERSITY COLLEGE LONDON Royaume-Uni Contribution nette de l'UE € 856 796,75 Adresse GOWER STREET WC1E 6BT London Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 856 796,75 KAROLINSKA INSTITUTET Suède Contribution nette de l'UE € 212 000,00 Adresse Nobels Vag 5 17177 Stockholm Voir sur la carte Région Östra Sverige Stockholm Stockholms län Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 212 000,00 VSEOBECNA FAKULTNI NEMOCNICE V PRAZE Tchéquie Contribution nette de l'UE € 80 000,00 Adresse U NEMOCNICE 2 12808 Praha 2 Voir sur la carte Région Česko Praha Hlavní město Praha Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 80 000,00