title: Folate metabolic gene polymorphisms and childhood acute lymphoblastic leukemia: a case-control study.
abstract: We genotyped six folate metabolic pathway genes for 11 polymorphisms in 460 cases of childhood acute lymphoblastic leukemia (ALL) and 552 ethnically matched controls. None of the polymorphisms except the 66A>G (I22M) in the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene showed any effect on disease risk. The carriers of the G-allele were associated with a marginal decreased risk of ALL (gender-adjusted global P=0.03; multiple-testing corrected P=0.25). Analysis of four polymorphisms in the MTRR gene showed statistically significant differences in haplotype distribution between cases and controls (global P<0.0001). The haplotypes GCAC (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.4-0.6) and ATAC (OR 0.5, 95% CI 0.3-0.6) were associated with a reduced risk and the haplotypes ACAC (OR 2.3, 95% CI 1.8-2.9) and GTAC (OR 1.8, 95% CI 1.4-2.3) with an increased risk. The genotype-combination analyses indicated that the best model stratifies cases and controls based on the 66A>G and the 524C>T polymorphisms in the MTRR gene (global P=0.03). Our results suggest that, besides a weak association of childhood ALL with the 66A>G polymorphism, haplotypes within the MTRR gene may, in part, account for population-based differences in risk.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Gast
authors.forename: J L
authors.initials: JL
authors.lastname: Bermejo
authors.forename: T
authors.initials: T
authors.lastname: Flohr
authors.forename: M
authors.initials: M
authors.lastname: Stanulla
authors.forename: B
authors.initials: B
authors.lastname: Burwinkel
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: C R
authors.initials: CR
authors.lastname: Bartram
authors.forename: K
authors.initials: K
authors.lastname: Hemminki
authors.forename: R
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012016:Reference Values
chemical_list: D004273:DNA, Neoplasm; D005492:Folic Acid