Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE)
Cancer Causes and Control,
Amigou A et al. – Maternal folic acid supplementation may reduce the risk of childhood AL. The findings also suggest that the genotype homozygous for any of the MTHFR variants and carrying both MTRR variants could be a risk factor for AL.
Methods- The nationwide registry-based case–control study, ESCALE, carried out in 2003–2004, included 764 AL cases and 1,681 controls frequency matched with the cases on age and gender.
- Information on folic acid supplementation was obtained by standardized telephone interview.
- The genotypes were obtained using high-throughput platforms and imputation for untyped polymorphisms.
- Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders.
- AL was significantly inversely associated with maternal folic acid supplementation before and during pregnancy (OR = 0.4; 95 % confidence interval: [0.3–0.6]).
- MTHFR and MTRR genetic polymorphisms were not associated with AL.
- However, AL was positively associated with homozygosity for any of the MTHFR polymorphisms and carriership of both MTRR variant alleles (OR = 1.6 [0.9–3.1]).
- No interaction was observed between MTHFR, MTRR, and maternal folate supplementation.



