title: Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Folate is involved in the one-carbon metabolism that plays an essential role in the synthesis, repair, and methylation of DNA. We examined whether child's germline genetic variation in the folate pathway is associated with childhood acute lymphoblastic leukemia (ALL), and whether periconception maternal folate and alcohol intake modify the risk.
  
  
  METHODS
  Seventy-six single nucleotide polymorphisms (SNPs), including 66 haplotype-tagging SNPs in 10 genes (CBS, DHFR, FOLH1, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS), were genotyped in 377 ALL cases and 448 controls. Log-additive associations between genotypes and ALL risk were adjusted for age, sex, Hispanic ethnicity (when appropriate), and maternal race.
  
  
  RESULTS
  Single and haplotype SNPs analyses showed statistically significant associations between SNPs located in (or adjacent to) CBS, MTRR, TYMS/ENOFS, and childhood ALL. Many regions of CBS were associated with childhood ALL in Hispanics and non-Hispanics (p < 0.01). Levels of maternal folate intake modified associations with SNPs in CBS, MTRR, and TYMS.
  
  
  CONCLUSIONS
  Our data suggest the importance of genetic variability in the folate pathway and childhood ALL risk.
authors: School of Public Health, University of California, Berkeley, 1995 University Avenue, Suite 460, Berkeley, CA 94704-7392, USA. cmetayer@berkeley.edu
authors: Catherine
authors: C
authors: Metayer
authors: Ghislaine
authors: G
authors: Scélo
authors: Anand P
authors: AP
authors: Chokkalingam
authors: Lisa F
authors: LF
authors: Barcellos
authors: Melinda C
authors: MC
authors: Aldrich
authors: Jeffrey S
authors: JS
authors: Chang
authors: Neela
authors: N
authors: Guha
authors: Kevin Y
authors: KY
authors: Urayama
authors: Helen M
authors: HM
authors: Hansen
authors: Gladys
authors: G
authors: Block
authors: Vincent
authors: V
authors: Kiley
authors: John K
authors: JK
authors: Wiencke
authors: Joseph L
authors: JL
authors: Wiemels
authors: Patricia A
authors: PA
authors: Buffler
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D005492:Folic Acid