Objective For this effort all top European cancer research groups working on the association between defects in the tricarboxylic acid cycle (TCAC) and cancer form a consortium to 1) profoundly characterize the human phenotypes to enable identification and efficient cancer prevention, and 2) to unravel the underlying molecular mechanisms. Recent breakthrough findings by the consortium participants and others have shown that defects in at least four TCAC genes - fumarate hydratase (FH, fumarase), and succinate dehydro genase (SDH) B, C, and D - can confer susceptibility to cancer. We shall take these studies forward by characterizing the natural history of the syndromes in large European materials. Simultaneously, we shall perform functional studies to elucidate the cel lular events induced by these defects by systems biology approaches including functional studies in cell lines, model organisms, and transcription profiling of TCAC deficient and proficient tumors and models. TCAC defect associated expression patterns will be utilized to examine other cancer types for such defects. We have evidence that modifying genes play a key role in TCAC defect associated tumorigenesis, and candidate regions have been identified. Following gene identification, the possible role of thes e modifiers in low penetrance cancer predisposition in the general population will be examined. The rationale to form this consortium is simple and strong. The consortium brings together the key European cancer researchers studying TCAC associated tumorige nesis. Studying separately the tumorigenic effects of FH and the different units of SDH would be ineffective, and formation of the consortium will ensure that Europe will maintain the initiative in this new and exciting field of research. The deliverables arising from the workpackages will contribute to the common goals; prevention of TCAC associated cancers, and learning the lessons these lesions can teach to cancer # Fields of science medical and health sciencesclinical medicineoncology Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2004-2.2.0-6 - Prevention, detection and treatment of familial cancers, such as cancer of the prostate, ovary, breast, colon and skin Call for proposal FP6-2004-LIFESCIHEALTH-5 See other projects for this call Funding Scheme STIP - Specific Targeted Innovation Project Coordinator HELSINGIN YLIOPISTO Address Yliopistonkatu 4 Helsingin yliopisto, helsinki Finland See on map Links Website Opens in new window EU contribution € 0,00 Participants (5) Sort alphabetically Sort by EU Contribution Expand all Collapse all INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL United Kingdom EU contribution € 0,00 Address 123 old brompton road London See on map Links Website Opens in new window LEIDEN UNIVERSITY MEDICAL CENTER Netherlands EU contribution € 0,00 Address Wassenaarseweg 72 Leiden See on map Links Website Opens in new window UNIVERSITAETSKLINIKUM FREIBURG Germany EU contribution € 0,00 Address Hugstetter straße 49 Freiburg See on map Links Website Opens in new window NATIONAL INSTITUTE OF CARDIOLOGY Poland EU contribution € 0,00 Address Alpejska 42 Warsawi See on map Links Website Opens in new window CANCER RESEARCH UK United Kingdom EU contribution € 0,00 Address 61, lincoln's inn fields London See on map Links Website Opens in new window
