The present study was designed to prospectively evaluate the role of the TT677 methylenetetrahydrofolate reductase (MTHFR) genotype, the prothrombin G20210A mutation, the factor V G1691A mutation, deficiencies of protein C, protein S, antithrombin, and increased lipoprotein (a) concentrations in leukemic children treated according to the ALL-Berlin-Frankfurt-Muenster (BFM) 90/95 study protocols with respect to the onset of vascular events.
This finding suggests gene-environment interaction and its role in the susceptibility to childhood ALL, which is consistent with previous findings associating either folate deficiency or MTHFR polymorphisms with risk of leukemia.
We hypothesized that a deactivating MTHFR allele would increase ALL relapse risk by potentially increasing 5,10-methylenetetrahydrofolate and dTMP, enhancing DNA synthesis and thus opposing MTX.
Our findings suggest that the MTHFR 677C>T and 1298A>C gene variants do not have a major influence on the susceptibility to pediatric ALL in the German population.
Further, at least two studies now show that the inactivating NAD(P)H:quinone acceptor oxidoreductase (NQO1) C609T polymorphism is positively associated with leukemias arising in the first 1-2 years of life and polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have been associated with adult and childhood ALL.
MTHFR genotypes were determined in DNA samples isolated from archived bone marrow smears of 15 patients with a second malignancy and a matched control group of 30 patients who did not developed a second malignancy after the treatment for ALL.
Methylenetetrahydrofolate reductaseC677T polymorphism: association with risk for childhood acute lymphoblastic leukemia and response during the initial phase of chemotherapy in greek patients.
In order to investigate the influence of two polymorphisms in the MTHFR gene, 677C>T and 1298A>C, on the risk of acute lymphoblastic leukemia (ALL) we performed a case-control study in children from different Brazilians' regions.
Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean population.
Although no consistent results on associations between MTHFR A 1298C polymorphism and ALL in the populations studied were obtained, the A1298C polymorphism, at least in Koreans, may be a genetic determinant among childhood ALL patients.
A meta-analysis of case-control studies that investigated the association between the C677T and/or A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and acute lymphoblastic leukemia (ALL) was carried out.
Most studies found a strong association between the polymorphisms MTHFR, C677T or A1298C, and NQO1*2 or *3 and the risk of acute lymphoblastic leukemia (ALL).
To provide a more robust estimate of the effect of MTHFR polymorphisms on the risk of ALL, we did a meta-analysis to reevaluate the association between the two most commonly studied MTHFR polymorphisms (C677T and A1298C) and ALL risk.
However, the MTHFR 677CT+TT genotype showed a tendency to be associated with adult ALL [crude odds ratio (OR), 0.67; 95% confidence interval (CI), 0.44-1.02; adjusted OR, 0.74 95% CI, 0.47-1.14].
NNMT IVS -151CC/MTHFR 677CT + TT patients exhibited a 2-fold reduction in ALL risk whereas RFC1 80AA/NNMT IVS -151CT + TT subjects had a 4.2-fold increase in ALL risk (P = .001).
Mutations in the MTHFR gene decrease the onset risk of ALL with relapse in the setting of no folate supplementation in pregnancy, but not of relapse-free ALL.