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Master Thesis

Analyse pharmacogénétique des voies du métabolisme des drogues utilisées dans le cancer du pancréas

Abstract : adenocarcinoma (ADK) of the pancreas. We want to evaluate the value of broad genotyping of drug metabolism genes in the response or severe toxicities occurrence taking into clinical and biological identified criteria in patients treated for pancreatic ADK. Materiel and Method: It’s a retrospective multicenter, feasibility study, evaluating the combination of genotyping data from the Affymétrix © DMET chip with the occurrence of haematological (HT), digestive toxicities or response. The clinico-biological criteria evaluated at diagnosis were lymphopenia, age >70 years, WHO status, severe malnutrition, deficiency of DPD (dihydropyrimidine dehydrogenase) or CDA (cytidine deaminase) deficiency. Patients were analyzed for all types of CT and then for each subgroup according to the treatment received. Results: 95 patients were analyzed in the "toxicity" cohort and 78 in the "response" cohort. Regardless of the type of CT prescribed 32 SNPs (single nucleotide polymorphisms) associated with occurrence toxicities or response were identified, 24 SNPs in gem- treated patients. monotherapy, 31 SNPs with FOLFIRINOX, 43 SNPs with SFU CT and 26 SNPs with gem.CT. Diagnosis lymphopenia was associated with the occurrence of HT > G2 in patients treated with 5SFU CT (p = 0.041) and global survival with any type of CT confounded (p = 0.016), severe malnutrition with TH > G2 under gem. alone (p = 0.018) or in combination (p = 0.044). Conclusion / Discussion: This preliminary work shows the feasibility and relevance of à comprehensive approach including clinical, biological and genetic criteria in association studies. À larger study is needed to identify the causal link and define predictive or prognostic factors.
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Submitted on : Monday, September 17, 2018 - 4:22:36 PM
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Julie Dahan. Analyse pharmacogénétique des voies du métabolisme des drogues utilisées dans le cancer du pancréas. Sciences du Vivant [q-bio]. 2017. ⟨dumas-01875687⟩



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