Doctor: Lucie Lecuyer

Title: Metabolomic signatures of long-term risk of breast and prostate cancers and diet in the SU.VI.MAX cohort : New insights from metabolomics applied to nutritional epidemiology

Supervisor: Mathilde Touvier

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

Date of thesis defense: 09/2019

Jury: Philippe Savarin

Thesis summary:

Breast and prostate cancers are among the cancers with the highest incidence worldwide and notably in Western countries. The main current challenges lie in the improvement of understanding of nutrition/health relationships and in the identification of individuals at higher risk long before the development of overt cancer to set up prevention actions. A variety of factors exert an impact on the onset and progression of cancer. Among these, nutrition appears as a key factor, in that it can be modified and acted upon through interventions. It is therefore crucial to assess its contribution. For this purpose,detailed and accurate assessment of nutritional intake is essential. Metabolomics, allowing the identification of endogenous, exogenous and microbial biomarkers, opens new perspectives in nutritional epidemiology. So far, few have studies investigated the impact of overall diet on metabolism and risk of breast and prostate cancer through metabolomic profiling. As part of this thesis, we conducted nested case-controls and cross-sectional studies within the SU.VI.MAX cohort to highlight plasma signatures of breast and prostate cancer risks and of overall diet. Plasma samples were collected at baseline and were analysed using two complementary methods : mass spectrometry coupled with liquid chromatography and proton nuclear magnetic resonance. Participants dietary habits were estimated using repeated 24h dietary records and socio-demographic and lifestyle data were collected from self-administered questionnaires.These investigations highlighted endogenous and microbial metabolites associated with overall diet as well as candidate biomarkers of specific dietary exposures. We also identified endogenous, exogenous and microbial metabolites associated with breast and prostate cancers risk suggesting a metabolic disruption up to 13 years before cancer diagnostic. Furthermore, diet appears to be implicated in the variation in plasma levels of some metabolites discriminating individuals at higher risk of developing breast or prostate cancers. These results need to be replicated in future independent observational and interventional studies. In the future, the identification of robust metabolic signatures of breast and prostate cancers risk, of the impact of diet on metabolism and carcinogenesis, and food intake would contribute to better understand health and environment relationships, to better estimate nutritional exposure or even to contribute to the set-up of new public health recommendations in order to reduce the incidence of these pathologies.

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