Genomics Biomarkers of Environmental Health

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1 Genomics Biomarkers of Environmental Health An FP7 molecular epidemiology project

2 EnviroGenomarkers is a European FP7 research project aiming at the development and application of a new generation of biomarkers, based on omics technologies, to study the environmental aetiology of human disease. The project uses omics technologies in a population study, aiming at: the discovery and validation of novel biomarkers predictive of increased risks of chronic diseases in which the environment may play an important role (breast cancer, Non Hodgkin s lymphoma, childhood diseases including allergy, neurological and immune diseases, thyroid disruption), the exploration of the association of such risk biomarkers with exposure to a number of high-priority or emerging environmental pollutants with carcinogenic, immunotoxic or hormone-like properties, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), cadmium, lead, phthalates, brominated flame retardants (polybrominated diphenyl ethers), ambient air pollutants and water treatment byproducts, the discovery and validation of biomarkers of exposure to the above environmental pollutants. Population study Case-control study nested within 3 prospective cohorts: The Northern Sweden Health and Disease Study (NSHDS, Umea, Sweden) EPIC Italy The Rhea mother-child birth cohort (Crete, Greece) Diseases and environmental chemicals Disease Breast cancer Non-Hodgkins lymphoma Chronic neurological, immune and allergy effects of childhood origin Chemical PCBs, PAHs, Cd PCBs PCBs, phthalates, polybrominated diphenyl ethers

3 Conceptual basis of the project 1. Biosamples and data from 3 prospective cohorts Northern Sweden Health and Disease Study 2. EPIC Italy 3. Rhea mother-child cohort (Crete, Greece) exposure Food frequency questionnaires Environmental monitoring GIS biomarkers of exposure Concentrations in urine, serum & erythrocytes DNA adducts intermediate -omics biomarkers of early effects Metabonomics Epigenomics Proteomics Transcriptomics disease Breast cancer Non-Hodgkin s lymphoma Childhood allergy, neurological and immune diseases chemicals: PCBs, PAHs, cadmium, phthalates, brominated flame retardants, ambient air pollutants, water disinfection byproducts Data integration using bioinformatics and systems biology methodologies Risk-predictive intermediate biomarkers Exposure risk predictive intermediate biomarkers relationships Exposure disease risk relationships Biomarker analyses 1. Intermediate, - omics biomarkers, using: Metabonomics, Epigenomics, Transcriptomics, Proteomics Bioinformatics and Systems Biology tools Biomarkers of exposure PCBs: serum concentrations of selected congeners using GC-MS/SIM cadmium: erythrocyte concentrations using ICP-MS PAHs: PAH-DNA adducts in blood leukocytes using ELISA phthalates: urine concentrations of selected congeners using HPLC/MS/ESI polybrominated diphenyl ethers: urine concentrations of selected congeners using GC/MS Other biomarkers SNPs and biomarkers of dietary micronutrients (available for part of the EPIC Italy & NSHDS subjects) Mammography data & hormone levels (available for part of the NSHDS subjects)

4 Exposure assessment Biomarkers of exposure Dietary exposure to nutrients and contaminants via Food Frequency Questionnaires GIS for air pollution (PM2.5, NOx) for EPIC-Italy and NSHDS, via the ESCAPE project; GIS for airborne PAHs, PCBs and cadmium (EPIC-Italy) Water disinfection byproducts for Rhea, via the Hi-Wate project Cohorts NSHDS - the Northern Sweden Health & Disease Study EPIC - Italy Rhea mother - child cohort Crete Cancer studies EPIC-Italy : samples (blood) collected from healthy subjects, years old, upto 15 years ago Northen Sweden Health and Disease Study: samples (blood) collected from healthy subjects, upto 30 years ago. Studies of neurological, immune diseases and allergy Rhea mother-child cohort, Crete: venous & cord blood from pregnant mothers; additional blood & urine samples from children at ages 2 and 4yrs; clinical tests on children at ages 2 and 4 yrs.

5 WP7 Management (Partner 1) Project structure Workpackages WP1 Cohorts (Partners 3,4,5,6) DATA WP3 Exposure assessment (Partners 1,4,5,6,7,9,10,11) SAMPLES DATA WP2 Intermediate biomarkers (Partners 1,2,3,7) WP4 Data warehousing and bioinformatics (Partners 2,3,10) WP5 Risk assessment and public health implications (Partners 1,3,4,5,6,7,8,10) WP6 Dissemination and Communication (Partner 1) Dissemination of knowledge The output of the project, especially the development and exploitation of novel, -omics-based biomarkers, is of strong interest for molecular epidemiology of environmental disease and for human biomonitoring. The project s results will be made known to the public and to policy makers, especially those associated with biomonitoring initiatives, such as DG Environment and DG SANCO. Impact The social impact of EnviroGenomarkers is expected to be high, since the project deals with issues such as Exposure to, and risks associated with, high priority and emerging pollutants Development of a new generation of biomarkers of exposure and of disease Cancer (breast and lymphomas) Neurological, immune system and allergy of childhood origin The development of new biomarkers of early effects, through the most advanced technology, will contribute to more effective human biomonitoring studies, to health protection and the formulation of preventive policies for European citizens. The scientific impact of the project is also significant as it opens the road to the exploitation, using modern-omics technologies, of thousands of biological samples stored in existing biobanks.

6 Partners: National Hellenic Research Foundation, Athens (S.A. Kyrtopoulos) Univ. of Maastricht (J. Kleinjans) Imperial College, London (P. Vineis) Umea University (I. Berghdahl) Istituto per lo Studio e la Prevenzione Oncologica, Florence (D. Palli) Univ. Crete (E. Stephanou ) Univ. Utrecht (R. Vermeulen) Istituto Superiore di Sanita, Rome (P. Comba) Natioal Institute for Health and Welfare, Kuopio (H. Kiviranta) Univ. of Leeds (M. Gilthorpe) Lund University (T. Lundh) Co-ordinator: S. Kyrtopoulos, Athens (skyrt@eie.gr) Project identity FP7 medium-scale collaborative project; priority area Environment (including climatic change), sub-activity Environment and health Grant Agreement Project duration: 3/2009-2/2013; Budget (EC contribution): 3.5 Meuro Design by Dimitra Pelekanou Photos Maria Botsivali Contact info: Dissemination Officer Dr. Maria Botsivali National Hellenic Research Foundation, Athens, Greece Tel: mbotsi@eie.gr

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