Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE)

Amigou, Alicia; Rudant, Jérémie; Orsi, Laurent; Goujon-Bellec, Stéphanie; Leverger, Guy; Baruchel, André; Bertrand, Yves; Nelken, Brigitte; Plat, Geneviève; Gautier, Michel; Haouy, Stèphanie; Chastagner, Pascal; Ducassou, Stéphane; Rialland, Xavier; Hémon, Denis; Clavel, Jacqueline

doi:10.1007/s10552-012-0004-0

Cited by 58 publications

(73 citation statements)

References 58 publications

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“…Consistent with our findings for the child's MTRR 66A>G genotype, four of seven previous studies reported at least some evidence of a protective effect of the mutant allele (24,(26)(27)(28). In addition, a meta-analysis of three studies assessing this polymorphism (26-28) reported summary ORs for AG and GG of 0.76 (95% CI, 0.60-0.96) and 0.67 (95% CI, 0.52-0.88), respectively (13).…”

Section: Discussionsupporting

confidence: 92%

“…For the MTHFR genotypes, however, a number of previous studies suggested that 677C>T may be protective, but that 1298A>C was not associated with risk (14, 15). We did not find evidence of a reduced risk with either polymorphism overall, similar to two recent studies (22,24).…”

Section: Discussionsupporting

confidence: 91%

“…Metayer and colleagues (25) recently reported evidence of interactions between maternal folic acid use and specific loci on the CBS, MTRR, and TYMS genes; however, these loci were not investigated in our study. A recent French study (24) reported no interactions, although results were not presented in the article.…”

Section: Discussionmentioning

confidence: 76%

“…[16][17][18][19][20][21][22][23], 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR; refs. 17,22,[24][25][26][27][28], methylenetetrahydrofolate dehydrogenase (MTHFD1; refs. 22,25,27,29), thymidylate synthetase (TS/ TYMS; refs.…”

Section: Introductionmentioning

confidence: 99%

“…A Californian study reported interactions between maternal folic acid use and filial genotype at specific loci on cystathionine-beta-synthase (CBS), MTRR, and TYMS genes (25), while a French study found no evidence of such interactions with polymorphisms in the MTHFR or MTRR genes (24).…”

Section: Introductionmentioning

confidence: 99%

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

Milne

Greenop

Scott

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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-

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Milne

Greenop

Scott

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Risk of neuroblastoma, birth‐related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE)

Rios

Bailey

Orsi

et al. 2016

Intl Journal of Cancer

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Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention.

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Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy

McKay

Adriaens

Evelo

et al. 2016

Molecular Nutrition Food Res

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ScopeEarly‐life exposures are critical in fetal programming and may influence function and health in later life. Adequate maternal folate consumption during pregnancy is essential for healthy fetal development and long‐term offspring health. The mechanisms underlying fetal programming are poorly understood, but are likely to involve gene regulation. Epigenetic marks, including DNA methylation, regulate gene expression and are modifiable by folate supply. We observed transcriptional changes in fetal liver in response to maternal folate depletion and hypothesized that these changes are concomitant with altered gene promoter methylation.Methods and resultsFemale C57BL/6J mice were fed diets containing 2 or 0.4 mg folic acid/kg for 4 wk before mating and throughout pregnancy. At 17.5‐day gestation, genome‐wide gene expression and promoter methylation were measured by microarray analysis in male fetal livers. While 989 genes were differentially expressed, 333 promoters had altered methylation (247 hypermethylated, 86 hypomethylated) in response to maternal folate depletion. Only 16 genes had both expression and methylation changes. However, most methylation changes occurred in genomic regions neighboring expression changes.ConclusionIn response to maternal folate depletion, altered expression at the mRNA level was not associated with altered promoter methylation of the same gene in fetal liver.

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Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE)

Abstract: The study findings support the hypothesis that maternal folic acid supplementation may reduce the risk of childhood AL. The findings also suggest that the genotype homozygous for any of the MTHFR variants and carrying both MTRR variants could be a risk factor for AL.

Cited by 58 publications

References 58 publications

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

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

Risk of neuroblastoma, birth‐related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE)

Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy

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