2019-05-292019-05-292017MOTA, Mayara Ferreira; VILHENA, Tayssa Cristina Lima de. Investigação de biomarcadores moleculares de medicina de precisão no gene DPYD como preditor de toxicidade a terapia com uso de fluoropirimidinas em pacientes com neoplasia gastrointestinal. Orientador: Ney Pereira Carneiro dos Santos. 2017. 64 f. Trabalho de Curso (Bacharelado em Medicina) - Faculdade de Medicina, Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém, 2017. Disponível em: https://bdm.ufpa.br/handle/prefix/1364. Acesso em:.http://bdm.ufpa.br/jspui/handle/prefix/1364Background:Fluoropyrimidinesare the main chemotherapy treatment of gastrointestinal tumors. However, approximately 30% of patients exhibit severe toxicities, leading to treatment discontinuation by toxicity and death. Biomarkers capable of predicting theoptimum time for onsetof treatment, combination of drugs to be chosen and minimally toxic-effective dose are essential guiding instruments. Purpose: To investigate association of molecular markers recommended by international agencies involved in the metabolic pathway of 5-FU: DPYD*2A (rs3918290), DPYD*5 (rs1801159), DPYD (rs17116806), DPYD (rs17376848), DPYD (rs1760217), DPYD (rs1801265), DPYD (rs4970722), DPYD (rs55886062), DPYD (rs67376768), with the toxicity profile to these drugin patients with gastrointestinal tumorsin the Brazilian’s northern region. Methods: A retrospective, cross-sectional, case-control was performed with evaluation of clinical and epidemiological data of 142 patients treated with fluoropyrimidines in monotherapy or combination. The TaqMan®system was used to investigate the DPYD polymorphisms. Results: The polymorphism rs3918290 showed a significant association with the presence of severe toxicities (grade 3-4), as well as the marker rs1801159 and the presence of diarrhea (p = 0.038). The polymorphic variants rs1801159 and rs4970722 showed a significant association for the development of neuropathy (p = 0.015 and p = 0.025, respectively). In addition, the polymorphisms rs17376848, rs4970722 and rs1801265 were statistically significant for the development of hematological reactions in patients treated with 5-FU (p = 0.043, p = 0.025 and rs1801265, p = 0.016). conclusion The data from this project corroborate with studies that sugest that polymorphisms in the DPYD gene are predictors of toxicities in cancer patients treated with fluoropyrimidines. However, there is a need for additional studies to reinforce the importance of clinical studies with 5-FU and oral fluoropyrimidines in miscegenated populations, such as the Brazilian population.Acesso AbertoDPYDCâncerFarmacogenéticaFluoropirimidinasCNPQ::CIENCIAS DA SAUDE::MEDICINATrabalho de Curso - Graduação - Monografia