ArticleProceedings of the National Academy of Sciences of the United States of America2001
Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 9 of them syntheses that pooled it.
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Who cites it
73 citing papers in PubMed, 9 syntheses or guidelines pooled it.
- Meta-prediction of MTHFR gene polymorphism-mutations, air pollution, and risks of leukemia among world populations.Oncotarget · 2017Pooled it
- The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case-control studies.Molecular biology reports · 2014Pooled it
- MTHFR gene polymorphism in acute lymphoblastic leukemia among North Indian children: a case-control study and meta-analysis updated from 2011.Journal of human genetics · 2014Pooled it
- MTHFR genetic polymorphisms may contribute to the risk of chronic myelogenous leukemia in adults: a meta-analysis of 12 genetic association studies.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Methylenetetrahydrofolate reductase polymorphisms and risk of acute lymphoblastic leukemia-evidence from an updated meta-analysis including 35 studies.BMC medical genetics · 2012Pooled it
- Candidate gene association studies and risk of childhood acute lymphoblastic leukemia: a systematic review and meta-analysis.Haematologica · 2010Pooled it
- A meta-analysis of the association between day-care attendance and childhood acute lymphoblastic leukaemia.International journal of epidemiology · 2010Pooled it
- A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in acute lymphoblastic leukemia.European journal of epidemiology · 2006Pooled it
- Update meta-analysis from biomedical literature about MTHFR'polymorphisms and the CML' risk.La Tunisie medicalePooled it
- The Interrelationship between Preconception Folate Nutritional Intake and Child Genetic Liability in the Risk of Childhood Acute Lymphoblastic Leukemia.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025Article
- Prenatal and Perinatal Factors Associated with Infant Acute Lymphoblastic Leukaemia: A Scoping Review.Cancers · 2025Review
- Review
- Association of Methylenetetrahydrofolate Reductase (Pediatric reports · 2024Article
- A gut instinct for childhood leukemia prevention: microbiome-targeting recommendations aimed at parents and caregivers.Frontiers in public health · 2024Review
- Susceptibility to hypertension based onFrontiers in cardiovascular medicine · 2023Article
- Periconceptional folate intake influences DNA methylation at birth based on dietary source in an analysis of pediatric acute lymphoblastic leukemia cases and controls.The American journal of clinical nutrition · 2022Article
- Large-scale screening for factor V Leiden (G1691A), prothrombin (G20210A), and MTHFR (C677T) mutations in Greek population.Health science reports · 2022Article
- Lack of Impact of the A1298C MTHFR on the Risk of Childhood Acute Lymphoblastic Leukemia: Evidence from a Meta-analysis.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2022Article
- Pharmacological mechanism of mylabris in the treatment of leukemia based on bioinformatics and systematic pharmacology.Bioengineered · 2021Article
- Maternal Haplotypes inGenes · 2019Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C-->T) and 1,298 (A-->C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15-0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07--0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20--1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia.
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