Objective 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. Keywords 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 Topic(s) ERC-2016-ADG - ERC Advanced Grant Call for proposal ERC-2016-ADG See other projects for this call Funding Scheme ERC-ADG - Coordinator UNIVERSITAET INNSBRUCK Net EU contribution € 1 115 793,00 Address Innrain 52 6020 Innsbruck Austria See on map Region Westösterreich Tirol Innsbruck Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (5) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITAET INNSBRUCK Austria Net EU contribution € 1 115 793,00 Address Innrain 52 6020 Innsbruck See on map Region Westösterreich Tirol Innsbruck Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITY COLLEGE LONDON HOSPITALSNHS FOUNDATION TRUST United Kingdom Net EU contribution € 233 251,25 Address Euston road 250 NW1 2PG London See on map Region London Inner London — West Camden and City of London Activity type Research Organisations Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITY COLLEGE LONDON United Kingdom Net EU contribution € 856 796,75 Address Gower street WC1E 6BT London See on map Region London Inner London — West Camden and City of London Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 KAROLINSKA INSTITUTET Sweden Net EU contribution € 212 000,00 Address Nobels vag 5 17177 Stockholm See on map Region Östra Sverige Stockholm Stockholms län Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 VSEOBECNA FAKULTNI NEMOCNICE V PRAZE Czechia Net EU contribution € 80 000,00 Address U nemocnice 2 12808 Praha 2 See on map Region Česko Praha Hlavní město Praha Activity type Research Organisations Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
