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Background  Acute lymphoblastic leukemia (ALL) is the most prevalent type of pediatric cancer, the causes of which are likely to involve an interaction between genetic and environmental factors. To evaluate the effects of the genotypic polymorphisms in methylenetetrahydrofolate reductase ( MTHFR ) on childhood ALL risk in Taiwan, two well-known polymorphic genotypes of  MTHFR , C677T (rs1801133) and A1298C (rs1801131), were analyzed to examine the extent of their associations with childhood ALL susceptibility and to discuss the  MTHFR  genotypic contribution to childhood ALL risk among different populations.    Methodology/Principal Findings  In total, 266 patients with childhood ALL and an equal number of non-cancer controls recruited were genotyped utilizing PCR-RFLP methodology. The  MTHFR  C677T genotype, but not the A1298C, was differently distributed between childhood ALL and control groups. The CT and TT of  MTHFR  C677T genotypes were significantly more frequently found in controls than in childhood ALL patients (odds ratios=0.60 and 0.48, 95% confidence intervals=0.42–0.87 and 0.24–0.97, respectively). As for gender, the boys carrying the  MTHFR  C677T CT or TT genotype conferred a lower odds ratio of 0.51 (95% confidence interval=0.32–0.81, P=0.0113) for childhood ALL. As for age, those equal to or greater than 3.5 years of age at onset of disease carrying the  MTHFR  C677T CT or TT genotype were of lower risk (odds ratio= 0.43 and 95% confidence interval=0.26–0.71, P=0.0016).    Conclusions  Our results indicated that the  MTHFR  C677T T allele was a protective biomarker for childhood ALL in Taiwan, and the association was more significant in male patients and in patients 3.5 years of age or older at onset of disease.

The Association of Methylenetetrahydrofolate Reductase Genotypes with the Risk of Childhood Leukemia in Taiwan