5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and the risk of acute lymphoblastic leukemia (ALL) in Filipino children.
BACKGROUND
5,10-Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism. Polymorphisms at the C677T and A1298C loci are associated with reduced activity; consequently more folate substrates are shunted toward thymidylate and DNA synthesis. Several studies have reported a reduced risk of developing ALL in children with MTHFR polymorphisms. The objective of this study was to determine the association between MTHFR polymorphisms and ALL in Filipino children.


METHODS
We conducted a case control study in children diagnosed with ALL at the Philippine General Hospital from 1/2001 through 12/2005. Bone marrow aspirate slides were reviewed by two expert hematologists to verify the morphologic diagnosis of ALL. DNA was isolated from the slides and MTHFR polymorphisms, C677T and A1298C, were determined using Taqman real-time PCR. Cord blood of healthy Filipino newborns served as control.


RESULTS
There were a total of 191 ALL and 394 controls genotyped. The distribution of C677T polymorphisms was similar in the two groups (P = 1.0). However, for A1298C, there was significantly more AC and CC genotypes in the ALL compared to controls (P = 0.02; OR 1.57; CI: 1.08-2.28). The 1298C allele frequency for the control group was 36.8% and 677T allele frequency was 9.9%.


CONCLUSIONS
A1298C polymorphisms is associated with an increased risk for ALL in Filipino children. This may be due to a difference in leukemia biology or to a high prevalence of folate deficiency in Filipinos. Our study reiterates the gene and environment interaction in leukemogenesis.
Alcasabas
Patricia
P
Section of Hematology-Oncology, Department of Pediatrics, Philippine General Hospital, Manila, Philippines. tricia_alcas@yahoo.com
Ravindranath
Yaddanapudi
Y
Goyette
Gerard
G
Haller
Andrew
A
Del Rosario
Luz
L
Lesaca-Medina
Maria Ysabel
MY
Darga
Linda
L
Ostrea
Enrique M
EM
Taub
Jeffrey W
JW
Everson
Richard B
RB
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012307:Risk Factors
D042965:Methylenetetrahydrofolate Reductase (NADPH2)