Research Article Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case–Control Study

Background: Recent research suggests that maternal folic acid supplementation is associated with a reduced risk of childhood brain tumors (CBT); polymorphisms in folate path-way genes could modify this association or directly influence CBT risk. Methods: Associations between risk of CBT and folate pathway polymorphisms were investigated in a population-based case– control study in Australia (2005–2010). Cases were recruited through all Australian pediatric oncology centers and controls by national random digit dialing. Data were available from 321 cases and 552 controls. Six polymorphisms were genotyped in children and parents (MTHFR 677C>T,MTHFR 1298A>C,MTRR 66A>G, MTR 2756A>G, MTR 5049C>A, and CBS 2199 T>C). Maternal folic acid use was ascertained via questionnaire. ORs were estimated using unconditional logistic regression. Case– parent trio analyses were also undertaken. Results: There was weak evidence of a reduced risk of CBT for the MTRR 66GG genotype in the child or father: ORs 0.71 [95 % confidence interval (CI), 0.48–1.07]; 0.54 (95 % CI, 0.34– 0.87), respectively. Maternal prepregnancy folic acid supple-mentation showed a stronger negative association with CBT risk where the child, mother, or father had theMTRR 66GG genotype (Pinteraction 0.07, 0.10, and 0.18, respectively). Conclusions: Evidence for an association between folate path-way genotypes andCBT is limited in this study. Therewas possible protection by theMTRR 66GG genotype, particularly when com-bined with maternal prepregnancy folic acid supplementation; these results are novel and require replication. Impact: The possible interaction between folic acid supple-mentation and MTRR 66A>G, if confirmed, would strengthen evidence for prepregnancy folate protection against CBT. Cancer Epidemiol Biomarkers Prev; 24(6); 931–7. 2015 AACR