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Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE).
Cancer Causes Control. 2012 Aug; 23(8):1265-77.CC

Abstract

PURPOSE

Fetal folate deficiency may increase the risk of subsequent childhood acute leukemia (AL), since folates are required for DNA methylation, synthesis, and repair, but the literature remains scarce. This study tested the hypothesis that maternal folic acid supplementation before or during pregnancy reduces AL risk, accounting for the SNPs rs1801133 (C677T) and rs1801131 (A1298C) in MTHFR and rs1801394 (A66G) and rs1532268 (C524T) in MTRR, assumed to modify folate metabolism.

METHODS

The nationwide registry-based case-control study, ESCALE, carried out in 2003-2004, included 764 AL cases and 1,681 controls frequency matched with the cases on age and gender. Information on folic acid supplementation was obtained by standardized telephone interview. The genotypes were obtained using high-throughput platforms and imputation for untyped polymorphisms. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders.

RESULTS

AL was significantly inversely associated with maternal folic acid supplementation before and during pregnancy (OR = 0.4; 95 % confidence interval: [0.3-0.6]). MTHFR and MTRR genetic polymorphisms were not associated with AL. However, AL was positively associated with homozygosity for any of the MTHFR polymorphisms and carriership of both MTRR variant alleles (OR = 1.6 [0.9-3.1]). No interaction was observed between MTHFR, MTRR, and maternal folate supplementation.

CONCLUSION

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.

Authors+Show Affiliations

Environmental Epidemiology of Cancer, INSERM U1018, Villejuif, France. alicia.amigou@inserm.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22706675

Citation

Amigou, Alicia, et al. "Folic Acid Supplementation, MTHFR and MTRR Polymorphisms, and the Risk of Childhood Leukemia: the ESCALE Study (SFCE)." Cancer Causes & Control : CCC, vol. 23, no. 8, 2012, pp. 1265-77.
Amigou A, Rudant J, Orsi L, et al. Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE). Cancer Causes Control. 2012;23(8):1265-77.
Amigou, A., Rudant, J., Orsi, L., Goujon-Bellec, S., Leverger, G., Baruchel, A., Bertrand, Y., Nelken, B., Plat, G., Michel, G., Haouy, S., Chastagner, P., Ducassou, S., Rialland, X., Hémon, D., & Clavel, J. (2012). Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE). Cancer Causes & Control : CCC, 23(8), 1265-77. https://doi.org/10.1007/s10552-012-0004-0
Amigou A, et al. Folic Acid Supplementation, MTHFR and MTRR Polymorphisms, and the Risk of Childhood Leukemia: the ESCALE Study (SFCE). Cancer Causes Control. 2012;23(8):1265-77. PubMed PMID: 22706675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE). AU - Amigou,Alicia, AU - Rudant,Jérémie, AU - Orsi,Laurent, AU - Goujon-Bellec,Stéphanie, AU - Leverger,Guy, AU - Baruchel,André, AU - Bertrand,Yves, AU - Nelken,Brigitte, AU - Plat,Geneviève, AU - Michel,Gérard, AU - Haouy,Stéphanie, AU - Chastagner,Pascal, AU - Ducassou,Stéphane, AU - Rialland,Xavier, AU - Hémon,Denis, AU - Clavel,Jacqueline, Y1 - 2012/06/16/ PY - 2012/02/14/received PY - 2012/05/24/accepted PY - 2012/6/19/entrez PY - 2012/6/19/pubmed PY - 2013/1/30/medline SP - 1265 EP - 77 JF - Cancer causes & control : CCC JO - Cancer Causes Control VL - 23 IS - 8 N2 - PURPOSE: Fetal folate deficiency may increase the risk of subsequent childhood acute leukemia (AL), since folates are required for DNA methylation, synthesis, and repair, but the literature remains scarce. This study tested the hypothesis that maternal folic acid supplementation before or during pregnancy reduces AL risk, accounting for the SNPs rs1801133 (C677T) and rs1801131 (A1298C) in MTHFR and rs1801394 (A66G) and rs1532268 (C524T) in MTRR, assumed to modify folate metabolism. METHODS: The nationwide registry-based case-control study, ESCALE, carried out in 2003-2004, included 764 AL cases and 1,681 controls frequency matched with the cases on age and gender. Information on folic acid supplementation was obtained by standardized telephone interview. The genotypes were obtained using high-throughput platforms and imputation for untyped polymorphisms. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders. RESULTS: AL was significantly inversely associated with maternal folic acid supplementation before and during pregnancy (OR = 0.4; 95 % confidence interval: [0.3-0.6]). MTHFR and MTRR genetic polymorphisms were not associated with AL. However, AL was positively associated with homozygosity for any of the MTHFR polymorphisms and carriership of both MTRR variant alleles (OR = 1.6 [0.9-3.1]). No interaction was observed between MTHFR, MTRR, and maternal folate supplementation. CONCLUSION: 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. SN - 1573-7225 UR - https://www.unboundmedicine.com/medline/citation/22706675/Folic_acid_supplementation_MTHFR_and_MTRR_polymorphisms_and_the_risk_of_childhood_leukemia:_the_ESCALE_study__SFCE__ L2 - https://doi.org/10.1007/s10552-012-0004-0 DB - PRIME DP - Unbound Medicine ER -