Abstract

<div>Abstract<p><b>Background:</b> Recent research suggests that maternal folic acid supplementation is associated with a reduced risk of childhood brain tumors (CBT); polymorphisms in folate pathway genes could modify this association or directly influence CBT risk.</p><p><b>Methods:</b> 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 (<i>MTHFR</i> 677C>T, <i>MTHFR</i> 1298A>C, <i>MTRR</i> 66A>G, <i>MTR</i> 2756A>G, <i>MTR</i> 5049C>A, and <i>CBS</i> 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.</p><p><b>Results:</b> There was weak evidence of a reduced risk of CBT for the <i>MTRR</i> 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 supplementation showed a stronger negative association with CBT risk where the child, mother, or father had the <i>MTRR</i> 66GG genotype (<i>P</i><sub>interaction</sub> = 0.07, 0.10, and 0.18, respectively).</p><p><b>Conclusions:</b> Evidence for an association between folate pathway genotypes and CBT is limited in this study. There was possible protection by the <i>MTRR</i> 66GG genotype, particularly when combined with maternal prepregnancy folic acid supplementation; these results are novel and require replication.</p><p><b>Impact:</b> The possible interaction between folic acid supplementation and <i>MTRR</i> 66A>G, if confirmed, would strengthen evidence for prepregnancy folate protection against CBT. <i>Cancer Epidemiol Biomarkers Prev; 24(6); 931–7. ©2015 AACR</i>.</p></div>

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