ED-10ASSOCIATIONS BETWEEN MATERNAL AND INHERITED GENETIC VARIATION IN FOLATE METABOLISM GENES AND PEDIATRIC BRAIN TUMORS IN A HIGH RISK POPULATION: A PILOT STUDY

ABSTRACT: Folic acid is critically important for normal neural development and has been implicated in pediatric brain tumor (PBT) risk. However, much work remains in understanding the genetic basis of these associations among at-risk populations. Therefore, we examined inherited variation in folate metabolism genes on PBT risk in individuals with Neurofibromatosis Type 1 (NF1), a cancer predisposition syndrome. We also evaluated maternal genetic variation in these genes that could serve as a proxy for the intrauterine nutrient environment that may be important in PBT development. We recruited 56 families with a child with NF1 and a PBT from the Washington University NF1 Patient Registry Initiative (NPRI) (https://nf1registry.wustl.edu/) or the St. Louis Children's Hospital Neurofibromatosis Clinical Program. DNA isolated from blood or buccal samples representing 45 triads (mother, father, child) and 11 dyads (mother, child) were analyzed using 49 tag single nucleotide polymorphisms (SNPs) genotyped on the Sequenom platform. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between maternal and offspring minor alleles and PBTs were estimated using log linear regression models. Significant/marginally significant associations between PBTs and each additional offspring copy of the minor allele were found for MTRR rs10520873 (OR = 0.5; 95% CI 0.3-1.0); MTR rs4659745 (OR = 0.5, 95% CI 0.2-0.9), rs3768147 (OR = 1.9; 1.1-3.3), rs12759827 (OR = 0.5, 95% CI 0.3-1.0); and DHFR rs10072026 (OR = 0.2; 95% CI 0.03-0.7). For maternal SNPs, significant/marginally significant associations were observed with each additional maternal copy of the minor allele for MTRR rs1802056 (OR = 1.94; 95% CI 1.1-3.6); SLC19A1 rs1051298 (OR = 2.0; 95% CI 1-3.4), rs2838957 (OR = 1.8; 1.0-3.4), rs4818789 (OR = 1.9; 95% CI 1.0-3.8), TYMS rs15872 (OR = 0.6; 95 %CI 0.3-1.0); and MTHFR rs3737964 (OR = 2.1; 95%CI 1.0-4.5) and rs1801133 (OR = 0.4; 95% CI 0.2-0.8). While our findings require validation, they suggest that inherited and maternal genetic variation in folate metabolic genes may influence PBT risk in children with NF1.

SUBMITTER: Johnson K 

PROVIDER: S-EPMC4218049 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature