title: 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.
abstract: 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.
authors.affiliation: Pharmacogenetics Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico.|Hematology Department, Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Myrna
authors.initials: M
authors.lastname: Candelaria
authors.affiliation: Hematology Department, Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Ojeda
authors.affiliation: Pharmacogenetics Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Olga
authors.initials: O
authors.lastname: Gutiérrez-Hernández
authors.affiliation: Pharmacogenetics Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Lucia
authors.initials: L
authors.lastname: Taja-Chayeb
authors.affiliation: Pharmacogenetics Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vidal-Millán
authors.affiliation: Instituto de Investigaciones Biomédicas, UNAM and Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Dueñas-González
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008727:Methotrexate / Q000008:administration & dosage* / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008800:Mexico; D008875:Middle Aged; D015999:Multivariate Analysis; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate