Folate Pathway Gene Polymorphisms, Maternal Folic Acid Use, and Risk of Childhood Acute Lymphoblastic Leukemia

Abstract

Background: Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003)(2004)(2005)(2006)(2007).Methods: All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched vari-

Maternal Haplotypes in DHFR Promoter and MTHFR Gene in Tuning Childhood Acute Lymphoblastic Leukemia Onset-Latency: Genetic/Epigenetic Mother/Child Dyad Study (GEMCDS)

“…Several studies and meta-analyses on the role of folate pathway gene variants in pediatric and adult acute leukemia focused on risk disease, treatment efficacy, and survival disclosing interesting pharmacogenetics considerations [36,37,38]. Less investigated in pediatric cancers is instead the mother-child dyad or parent-child triad approach [39,40,41,42]. The present study was conducted within the frame of the GEMCDS study aimed to recognize any genetic and epigenetic factor with prognostic role and effect on any aspect of childhood ALL.…”

The association between methionine synthase A2756G polymorphism and hematological cancer

“…Some studies have found an increased risk of hematological cancer was associated with the 2756G allele, [ 16 , 37 ] some studies identified a reduced risk, [ 19 , 21 , 28 , 35 , 38 ] and another did not detect the association between them. [ 14 , 15 , 17 , 18 , 20 , 22 – 27 , 29 – 34 , 36 ] To resolve these conflicting findings, we conducted a meta-analysis including 26 studies. Overall, we failed to find any statistical evidence for the MS A2756G polymorphism and susceptibility with hematological cancer under the homozygote, heterozygote, dominant, and recessive models, respectively.…”

Maternal Red Blood Cell Folate and Infant Vitamin B12 Status Influence Methylation of Genes Associated with Childhood Acute Lymphoblastic Leukemia

“…This finding was supported by the largest meta‐analysis to date, which observed that folate supplementation preconception reduces ALL risk (OR: 0.69, 95% CI: 0.50–0.95) . Furthermore, genetic studies investigating the influence of both parental and offspring variants of folate‐metabolizing genes on childhood ALL risk corroborate the hypothesis that lower folate status may enhance disease risk . The observational evidence that in utero folate exposure may modulate risk of childhood ALL development is consistent but, to date, there is limited insight into the underlying mechanism through which folate status prior to, and during, pregnancy may be involved in disease development.…”