Navegando por Autor "FERNANDES, Marianne Rodrigues"

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Acesso aberto (Open Access)
Associação do perfil de acetilação lenta do gene NAT2 na susceptibilidade ao câncer, na Região Norte do Brasil
(Universidade Federal do Pará, 2013-04-10) FERNANDES, Marianne Rodrigues; SANTOS, Ney Pereira Carneiro dos; http://lattes.cnpq.br/1290427033107137; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099
Objectives: The N-acetyltransferase 2 (NAT2) gene is a marker for the study of interindividual susceptibility to develop malignant neoplasms, once the enzyme NAT2 takes part in the metabolism of carcinogenic agents and the single nucleotide polymorphism (SNP) of its gene produces enzymes with different activities, leading to either slow or fast acetylation of xenobiotics. The purpose of this study was to investigate a possible association between the NAT2 gene SNPS and susceptibility to the involvement of gastric adenocarcinoma or invasive ductal carcinoma of the breast in patients of northern Brazil. Methods: Five polymorphisms of great importance for defining the metabolism profile of enzyme NAT2 (C282T, T341C, C481T, A803G and G857A) were investigated by direct sequencing of 986 base pairs, amplified in two PCR reactions, totalizing 133 patients with neoplasms (63 with Gastric Cancer-GC and 70 with Breast Cancer-BC) and 89 Control subjects. In order to avoid spurious interpretations resulting from the population substructure, we used a panei with 48 ancestry informative markers (AIM). Results: We found statistical differences for African and European parental contribution when compared between the Cancer and Control groups; a higher African contribution was detected in the study group with Cancer and, in the control group, it was detected a higher European contribution (p<0.001). Dominating polymorph genotypes C282T (TT + CT) showed significant association (p<0.001; OR 3.076; Cl 95% 1.664-5.687) for susceptibility to the different forms of Cancer investigated. A significant association of slow and fast acetylation profile with the susceptibility to develop the investigated neoplasms was noticed (p=0.010; OR 3.054; Cl 95% 1.303-7.159) and (p= 0.041; OR 0.527 Cl 95% 0.280-0.973) clearly showing that individuais with slow acetylator profile showed a risk of developing neoplasms increased to up to three times when compared to Control subjects. Conclusions: Ancestry genomic control was effectively important for this investigation and enabled the control of the ancestry effect on the association of NAT2 gene for susceptibility to cancer. In this study, it was possible to prove the strong influence of xenobiotics slow acetylation profile on the susceptibility to GC and BC.
Acesso aberto (Open Access)
Farmacogenômica das fluoropirimidinas no tratamento oncológico personalizado
(Universidade Federal do Pará, 2016-12-29) FERNANDES, Marianne Rodrigues; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099
Recently, cancer has become an obvious public health problem worldwide. The Fluoropyrimidine-based regimen has been the most widely used chemotherapy regimen worldwide in several types of solid tumors, including gastric and colorectal cancer. Of the total number of patients treated with 5-Fluorouracil (5-FU), 10-40% have severe toxicities, which usually result in prolonged and costly hospitalizations. The principle of personalized medicine is to study responses to medications based on individual genomic information. The high degree of miscegenation is a challenge for the worldwide implementation of personalized medicine in clinical practice. Many studies in the specialized literature have reported the influence of pharmacogenomic markers in mixed populations such as the Brazilian population. The aim of this study was to investigate the pharmacogenomic variability of different biomarkers in pharmacogenes involved in the metabolism pathway of Fluoropyrimidines in patients with gastric cancer or colorectal cancer, which are sub-strutured according to response and toxicity to treatment. To perform the research we used 216 patients with colorectal or gastric cancer who received 5-FU chemotherapy treatment. We investigated 33 genetic polymorphisms in 17 pharmacogens (ABCB1, ABCC2, ABCC4, ABCG2, CYP2A6, DPYD, FPSG, ITGB5, MTHFR, SLC22A7, SLC29A1, TP53, TYMS, UMPS, GGH, RRM1, TYMP) involved in the metabolism pathway of fluoropyrimidines. Our results showed that 77.3% of the patients presented some type of toxicity related to 5-FU treatment, of which 22% presented severe toxicities classified in grade 3 and 4. Death occurred in 23 patients, where three cases were related to toxicity and four cases with tumor progression and chemotherapeutic toxicity. Population substructuration was not influential in the association results for pharmacogenetic polymorphisms with the use of 5-FU. The FPGS gene (rs4451422) was shown to be significant in association with overall toxicity (p = 0.0052; OR 0.32) and toxicity events (p = 0.0004; OR 0.22). The ABCC4 gene (rs148551) had a significant association with the clinical response (p = 0.0056; OR 0.28). The SLC29A1 gene (rs760370) was shown to be significant for grade 3 and 4 toxicities (p = 0.0033; OR 4.73). In conclusion, due to the high degree of miscegenation in the Brazilian population, and particularly in the North of Brazil, the generated 5-FU pharmacogenomics data are particularly unique when compared to the homogenous populations investigated to date. The ABCC4, FPGS and SLC29A1 genes have been shown to be important biomarkers predictive of personalized medicine therapy using 5-FU.