SUJET DE STAGE N° 5
Transcription
SUJET DE STAGE N° 5
Master 2 R et P : Spécialité MRESTE Méthodes de Recherche en Environnement - Santé – Toxicologie - Ecotoxicologie Mention ISM, Ingénieries pour la Santé et le Médicament Responsable : Pr Anne MAITRE : TIMC-EPSP, UJF/UFR Médecine, CHU Grenoble Référent Toxicologie et Modélisation : Dominique BICOUT : TIMC-EPSP, UJF/VETAGROSUP Lyon Référent Ecotoxicologie : Muriel RAVETON : LECA-P3E, UJF/UFR Biologie SUJET DE STAGE N° 5 Research team and laboratory: EPSP team, TIMC laboratory (UMR 5525), UJF Universitary supervision: Vincent Bonneterre / Dominique Bicout ([email protected]) For information, a neurologist, Dr Emmeline Lagrange is associated to the project. Applicant: must have a strong interest in environmental health determinants and Geographic Information System TITLE : ALS neurodegenerative disease and selenium content in drinking water : investigation of spatial correlations BACKGROUND. Disease: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of the motor system (upper and lower motoneurones), relentlessly progressive and fatal. Behind this odd name, “Amyotrophic” refers to the main clinical feature of muscles wasting leading to progressive paralysis (limbs, speech, swallowing and respiration), and “lateral sclerosis” to the pathological examination of spinal cord of autopsied patients. Overall population-based lifetime risk of ALS is 1:400 for women and 1:350 for men. With more classical epidemiological indicators, the incidence is 2.2/ 100 000 person-year in Europe, the peak age about 60. The median survival of 30 months only. Hundred and sixty years after its description by Charcot, the treatment remains mainly supportive / palliative… Etiology: the disease still of unknown etiology for 90-95% of the cases that are not familial. Indeed, there is still controversy about the potential behavioural, occupational and environmental risk factors that have been studied (Physical activity, Gulf war veterans, selenium in drinking water, heavy metals, « Farming » and « pesticides », electromagnetic fields, history of electrical shocks, neurotoxins including the cyanotoxin BMAA, and infectious agents). Expertise of supervisors: We belong to a consortium which realized (2012) the wider incidence study on ALS in France, as part of a research project funded by French Research Agency. Our cases were geolocalised and we were able to identify geographic clusters of ALS patients. We made the hypothesis that clusters could help to shade the light on places where ALS-related environmental factors, if they exist, could be more easily brought to the fore. We are currently testing the BMAA hypothesis, and will now test the selenium one OBJECTIVE. This master’s main objective is to test, if there is a spatial correlation between patient location and selenium concentrations in drinking water, as this has been described once in a nearby region of Italy. Secondary objectives are to duplicate the analysis with other trace metals which concentrations are also available METHOD. Population: 649 ALS cases (2003-2011) from a French area covering 3.1 millions inhabitants (administrative districts).The file with patients geolocalisation is available. Exposures: Selenium and other trace metals content in drinking water for each water distribution unit (SISEEAUX database). Methods and software: Use of geostatistical tools (ArcGis V9 or V10) EXPECTED RESULTS. A submission of the results in an international scientific journal is expected in June 2014. Secrétariat pédagogique : [email protected] UFR de Médecine – Domaine de la Merci – 38706 La Tronche cedex – France - Tél : (0)4.76.63.75.01 – Fax : (0)4.76.63.75.02 KEY WORDS : Geoepidemiology, Ecological study, Selenium, Neurodegenerative disease DOMINANT CHARACTERISTICS Data handling and analyses Some references : About Disease: Kiernan et al. Amyotrophic Lateral Sclerosis. Lancet, 2011; 377:942-955 About suspected risk factors, especially Selenium: Vinceti M, et al. Are environmental exposures to selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis? Rev Environ Health. 2012;27(1):19-41. About ALS and Metal hypothesis more generally: Garruto, Yanagihara, Contributions of isolated Pacific populations to understanding neurodegenerative diseases. Folia Neuropathologica 2009;47(2)149-170 About Selenium content in drinking water in France: ANSES note : « Avis relatif à l’évaluation des risque sanitaires liés aux dépassement de la limite de qualité du sélénium dans les eaux destinées à la consommation humaine”. Octobre 2012. Saisine n° 2011-SA-0220