Folate pathway gene polymorphisms, maternal folic acid use and risk of childhood acute lymphoblastic leukemia
Menée en Australie auprès de 392 cas et 535 témoins, cette étude évalue l'association entre sept polymorphismes de gènes de la voie métabolique des folates, une supplémentation maternelle en acide folique pendant la grossesse et le risque de leucémie lymphoblastique aiguë chez l'enfant
Background: Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007). Methods: All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68 and CBS 2199 T>C) were genotyped in children and their parents. Information on pre-pregnancy maternal folic acid supplement use was collected. Odds ratios (ORs) were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed. Results: There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 (95% CI 0.39, 0.91) and 0.64 (95% CI 0.40, 1.03) respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI 1.02, 1.93) and 1.81 (95% CI 1.06, 3.07). ORs varied little by maternal folic acid supplementation. Conclusions: Some folate-pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation. Impact: Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results.