Gene-gene interactions in the folate metabolic pathway influence the risk for acute lymphoblastic leukemia in children.
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Genetic polymorphisms in the folate metabolic pathway may contribute to the susceptibility to childhood ALL because they affect the DNA synthesis, methylation and repair. We analysed common genetic polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), methionine synthase (MS) and methionine synthase reductase (MTRR) in 68 children with ALL and 258 healthy controls to investigate their influence on the risk for ALL. No significant differences in frequencies of separate polymorphisms were observed between both groups. Combined MTHFR 677CT/TT and MS 2756AG/GG genotypes showed a nonsignificant tendency to reduce the risk for ALL 2.24-fold (CI: 0.191 - 1.037, P: 0.061). The risk was significantly reduced in carriers of combined MTHFR 677CT/TT, MS 2756AG/GG and MTRR 66AG/GG genotypes (OR: 0.312; CI: 0.107 - 0.907; P: 0.032). Our results suggest that gene - gene interactions that may decrease the methylation capacity might have a protective effect on the risk for childhood ALL.
Petra
Bohanec Grabar
BG
Institute of Biochemistry, University of Ljubljana, Ljubljana, Slovenia.
Janez
Jazbec
J
Vita
Dolzan
D
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism*; D025941:Protein Interaction Mapping; D012306:Risk
D005492:Folic Acid