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. Pooled odds ratios (OR) of various
genetic contrasts of each polymorphism were estimated using random (RE)
and fixed effects (FE) models. Pooled ORs for combined genotypes and
haplotypes were estimated after adjustment for study effect using a
log-linear model and the expectation-maximization algorithm in
combination with log-linear modeling, respectively. The recessive model
for allele 1298C produced a rather marginal association: RE OR: 0.67;
95% confidence interval (CI): 0.46-0.99 and FE OR: 0.64; 95% CI:
0.49-0.84. In Caucasians, the results of the recessive model for allele
1298C was consisted with a protective effect of ALL development: FE OR:
0.63; 95% CI: 0.46-0.87. In childhood ALL, according to the results of
the allele contrast and the recessive model for 677T allele it was
conceivable that a protective effect exist: RE OR = 0.74; 95% CI:
0.57-0.96 and RE OR: 0.69; 95% CI: 0.51-0.94, respectively. The
combined genotypes produced significant pooled OR for the 677CC/1298CC
relative to 677CC/1298AA (OR: 0.54; 95% CI: 0.36-0.80). The haplotype
677C/1298C might be more protective to ALL relative to haplotype
677C/1298A (OR: 0.77; 95% CI: 0.61-0.97). When studies not in
Hardy-Weinberg equilibrium (HWE) were corrected to account for
departures from HWE, then, the pattern of results remained the same.
Overall, there is high heterogeneity between the studies in both
polymorphisms. A differential magnitude of effect in large versus small
studies and alteration of early extremes effects existed