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Abstract

G80A Single Nucleotide Polymorphism in Reduced Folate Carrier-1 Gene in a Mexican Population and its Impact on Survival in Patients with Acute Lymphoblastic Leukemia

VOLUME 68 - NUMBER 3 / May - June (Original articles)

Myrna Candelaria-Hernández, Research Division, Instituto Nacional de Cancerología (INCan), Mexico City
Juan Ojeda, Hematology Department, Mexico City, Mexico
Olga Gutiérrez-Hernández, Research Division, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
Lucia Taja-Chayeb, Research Division, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
Silvia Vidal-Millán, Pharmacogenetics Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico
Alfonso Dueñas-González, Instituto de Investigaciones Biomédicas, UNAM and Instituto Nacional de Cancerología, Mexico City, Mexico

Background: Hyper-CVAD is the treatment for patients with acute lymphoblastic leukemia in our institution. Objective: To evaluate the impact of single nucleotide polymorphisms at genes associated with methotrexate metabolism on survival. Methods: The presence of the single nucleotide polymorphisms G80A at reduced folate carrier-1 gene and C677T in the methylenetetrahydrofolate reductase gene was determined by denaturing high performance liquid chromatography and validated by sequencing. Both single nucleotide polymorphisms were evaluated in 71 healthy donors and in an exploratory pilot trial with acute lymphoblastic leukemia patients to determine the influence of these single nucleotide polymorphisms on clinical outcome. Clinical characteristics, response, and outcome were registered. A Cox regression analysis was done to evaluate factors influencing response and overall survival. Results: There were no differences in the frequency of single nucleotide polymorphisms between volunteers and acute lymphoblastic leukemia patients according to the Hardy-Weinberg test. Sensitivity and specificity were 72 and 91% for the G80A, and 64 and 75% for the C677T, respectively. The multivariate analysis showed that the T-immunophenotype and the presence of single nucleotide polymorphism G80A reduced folate carrier-1 were associated with a shorter relapse-free survival and overall survival. Conclusions: The presence of G80A single nucleotide polymorphism at reduced folate carrier-1 gene in acute lymphoblastic leukemia patients was associated with a poorer prognosis.

Keywords: RFC1 gene. MTHFR4 gene. SNP. Leukemia. Methotrexate.

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