title: A case-parent triad assessment of folate metabolic genes and the risk of childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  We conducted a case-parent triad study evaluating the role of maternal and offspring genotypes in the folate metabolic pathway on childhood acute lymphoblastic leukemia (ALL) risk.
  
  
  METHODS
  Childhood ALL case-parent triads (n = 120) were recruited from Texas Children's Hospital. DNA samples were genotyped using the Sequenom iPLEX MassARRAY for 68 tagSNPs in six folate metabolic pathway genes (MTHFR, MTRR, MTR, DHFR, BHMT, and TYMS). Log-linear modeling was used to examine the associations between maternal and offspring genotypes and ALL.
  
  
  RESULTS
  After controlling for the false discovery rate (<0.1), there were 20 significant maternal effects in the following genes: BHMT (n = 3), MTR (n = 12), and TYMS (n = 5). For instance, maternal genotypes for BHMT rs558133 (relative risk [RR] = 0.51, 95 % confidence interval [CI]: 0.30-0.87, p = 0.008, Q = 0.08) and MTR rs2282369 (RR = 0.46, 95 % CI: 0.27-0.80, p = 0.004, Q = 0.08) were associated with ALL. There were no significant offspring effects after controlling for the false discovery rate.
  
  
  CONCLUSIONS
  This is one of the few studies conducted to evaluate maternal genetic effects in the context of childhood ALL risk. Furthermore, we employed a family-based design that is less susceptible to population stratification bias in the estimation of maternal genetic effects. Our findings suggest that maternal genetic variation in the folate metabolic pathway is relevant in the etiology of childhood ALL. The observed maternal genetic effects support the need for continued research of how the uterine environment may influence risk of ALL.
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.forename: Darryl
authors.initials: D
authors.lastname: Nousome
authors.forename: Kala Y
authors.initials: KY
authors.lastname: Kamdar
authors.forename: M Fatih
authors.initials: MF
authors.lastname: Okcu
authors.forename: Michael E
authors.initials: ME
authors.lastname: Scheurer
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D005492:Folic Acid