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Understanding cancer development in BRCA 1/2 mutation carriers for improved Early detection and Risk Control

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.

Call for proposal

ERC-2016-ADG
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Host institution

UNIVERSITAET INNSBRUCK
Address
Innrain 52
6020 Innsbruck
Austria
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 115 793

Beneficiaries (5)

UNIVERSITAET INNSBRUCK
Austria
EU contribution
€ 1 115 793
Address
Innrain 52
6020 Innsbruck
Activity type
Higher or Secondary Education Establishments
UNIVERSITY COLLEGE LONDON HOSPITALSNHS FOUNDATION TRUST
United Kingdom
EU contribution
€ 233 251,25
Address
Euston Road 250
NW1 2PG London
Activity type
Research Organisations
UNIVERSITY COLLEGE LONDON
United Kingdom
EU contribution
€ 856 796,75
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 212 000
Address
Nobels Vag 5
17177 Stockholm
Activity type
Higher or Secondary Education Establishments
VSEOBECNA FAKULTNI NEMOCNICE V PRAZE
Czechia
EU contribution
€ 80 000
Address
U Nemocnice 2
12808 Praha 2
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)