%0 Journal Article
%T Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia
%A Dayse Maria Vasconcelos de Deus
%A Elker Lene Santos de Lima
%A Rafaela Maria Seabra Silva
%A Edinalva Pereira Leite
%A Maria Tereza Cartaxo Muniz
%J Leukemia Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/292043
%X The influence of genic polymorphisms involved in metabolism of chemotherapeutic agents as the methotrexate (MTX) has been studied mainly in acute lymphoblastic leukemia (ALL) of childhood. Advances in treatment may be attributed to identification of prognostic factors added to chemotherapy protocol. The aim of this study was to analyze the association of the C677T, A1298C, and G80A polymorphisms on MTHFR gene and on the overall survival of pediatric patients with lymphoblastic leukemia treated with MTX according to the Brazilian protocol in 187 months. The C677T and G80A polymorphisms were genotyped by PCR-RFLP and A1298C polymorphism by allele-specific PCR. We observed that ALL patients presented rate (dead/alive) of 0.36 for the 677CC genotype, corresponding also to lower overall survival ; on the other hand, the 677TT genotype showed a better survival (98%). Thus, we believe that patients with 80AA genotype presented a small reduction in MTX plasma level, suggesting that ALL children, carrying the 80AA genotype, showed a high toxicity to MTX . 1. Introduction Leukemia is the most common childhood cancer. Recently the influence of polymorphisms in different genes is involved on the metabolism of chemotherapeutic agents and it has been studied especially in childhood acute lymphoblastic leukemia (ALL) [1]. Despite actual chemotherapy protocols cure almost 80% of pediatric patients with ALL, the majority of adult patients still die from this disease. Advances in cure rates in children could be attributable to identification of prognostic features together with the intensified chemotherapy and improved supportive therapy [2]. Genetic polymorphisms in patients with ALL can alter drug-metabolizing enzymes, transporters, and targets; therefore, they can influence both efficacy and toxicity of chemotherapeutic agents. Actually this type of genetic polymorphisms is not used in a specific treatment; however, they could be responsible for an altered sensitivity of leukemic cells to drugs [3]. The pharmacological pathway of MTX is useful to identify genes and polymorphisms that influence the response to chemotherapy for ALL. An important enzyme in the folate/methotrexate metabolism pathway is 5,10-methylenetetrahydrofolate reductase (MTHFR), which catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate in the folic acid cycle [3]. The MTHFR plays an important role in the folate metabolism and differences in its activity due to these two genic variants might modify the modulation of therapeutic response to antifolate
%U http://www.hindawi.com/journals/lrt/2012/292043/