title: Influence of Methylenetetrahydrofolate Reductase C677T, A1298C, and G80A Polymorphisms on the Survival of Pediatric Patients with Acute Lymphoblastic Leukemia.
abstract: 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 (n = 126) 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 (P = 0.0013); 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 (P < 0.0001).
authors.affiliation: Pediatric Hematology Oncology Center (CEONHPE), UPE, Avenida Agamenon Magalhães, Bairro de Santo Amaro, 50100-010 Recife, PE, Brazil ; Department of Tropical Medicine, Federal University of Pernambuco (UFPE), Avenida Moraes Rego, 1235 University City, 50670-901 Recife, PE, Brazil.
authors.forename: Dayse Maria Vasconcelos
authors.initials: DM
authors.lastname: de Deus
authors.forename: Elker Lene Santos
authors.initials: EL
authors.lastname: de Lima
authors.forename: Rafaela Maria
authors.initials: RM
authors.lastname: Seabra Silva
authors.forename: Edinalva Pereira
authors.initials: EP
authors.lastname: Leite
authors.forename: Maria Tereza
authors.initials: MT
authors.lastname: Cartaxo Muniz