Étude pharmacogénétique du cancer du sein

Abstract

Personalized medicine is a concept designed to adapt the treatment of pathology to each individual through a better knowledge of the causes of inter-individual variabilities. In the domain of oncology, the finding of great variability in the response to a drug, in terms of efficacy and toxicity, is far to be new. This inter-individual variability can come from genetic polymorphisms involved in the kinetics of drugs. Some SNPs are suggested to be associated with improved or reduced efficacy of treatment. The aim of this study was to search for molecular markers that were predictive of the most effective chemotherapy regimens in breast cancer. We studied the contribution of polymorphisms IVS14 + 1G> A of DPYD gene, A313G of GSTP1 gene, C677T and A1298C of MTHFR gene, G2677T/A and C3435T of ABCB1 gene in response to FAC or FEC breast cancer’s chemotherapy. Our cohort included 117 patients. Treatment outcomes were evaluated and genotyping of the various polymorphisms was carried out by RFLP PCR and direct sequencing. Our study confirms that there is a significant correlation between the polymorphisms IVS14 + 1G> A of DPYD gene, C677T of MTHFR gene and response to treatment (p˂0.05). These results confirm the value of these polymorphisms as predictors of the efficacy of FAC or FEC chemotherapeutic treatments for breast cancer patients and, therefore, the benefit of a pharmacogenetic approach to identify new prognostic and predictive biomarkers, with a view to personalized treatment.