Doctor: Pauline Rebouillat

Title: An epidemiological approach to the associations between dietary exposure to pesticides and chronic diseases : new perspectives with integration of food production systems

Supervisor: Emmanuelle Kesse-Guyot

Doctoral school: ED 146 Doctoral school Galilée, University Sorbonne Paris Nord

Date of thesis defense: 09/2021

Jury: Cécilia Samieri, Laurence Guldner-Leplatois, Pierre Lombrail

Thesis summary:

Some pesticides, used in large quantities in current European agricultural practices, are suspected of having harmful effects on human health (cancers, metabolic diseases, neurodegenerative diseases). While occupational exposure is now well documented, data on the exposure of the general population to these molecules, mainly through dietary route are lacking. The aim of this work was to identify dietary pesticide exposure profiles, taking into account the production system (“conventional” or organic agriculture), and then to study the associations between these exposure profiles and various chronic diseases (breast cancer, type 2 diabetes). In 2014, participants of the NutriNet-Santé cohort completed a self-administered semi-quantitative food frequency questionnaire, assessing conventional and organic food consumption separately. Exposures to 25 active substances used in plant protection products in the European Union were estimated using a pesticide residue database considering agricultural practices from the Chemisches und Veterinäruntersuchungsamt Stuttgart, Germany. Non-negative Matrix Factorisation (NMF), especially relevant for data with excess zeros, was used to establish exposure profiles. For the characterisation step, the resulting NMF components were then introduced into a hierarchical clustering process resulting into 6 clusters. For the study of associations with breast cancer and diabetes, the four NMF components obtained were divided into quintiles and then introduced into Cox models adjusted for known confounders. Cancer and diabetes cases were identified through a multi-source strategy including linkage with medico-administrative databases. The characterisation of the clusters revealed a similar exposure in terms of molecules, with a gradient throughout the clusters, linked to the proportion of organic food in the diet. Associations between chronic diseases and NMF components were found: on one hand, associations between NMF component 3, reflecting low exposure to synthetic pesticides, and decreased risks of post-menopausal breast cancer and type 2 diabetes; on the other hand, associations between NMF component 1 (strongly correlated to several synthetic pesticides) and increased risks of post-menopausal breast cancer and type 2 diabetes. These findings suggest a potential role of dietary pesticide exposure on chronic diseases risk. Further research is needed to investigate the mechanisms and confirm these findings in other populations. Ultimately, these results could have important implications for the development of prevention strategies, through regulations or dietary guidelines.

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