ArticleInternational journal of cancer2009
The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification.
Article in International journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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Who cites it
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 87 citations in OpenAlex.
- Germline and somatic genetic predictors of pathological response in neoadjuvant settings of rectal and esophageal cancers: systematic review and meta-analysis.The pharmacogenomics journal · 2016Pooled it
- Pooled it
- Dissecting pleiotropy to gain mechanistic insights into human disease.Nature reviews. Genetics · 2026Review
- Relationship between MTHFR gene polymorphism and risk of thrombosis in postoperative patients with colorectal cancer.Experimental and therapeutic medicine · 2023Article
- The evolution of human skin pigmentation: A changing medley of vitamins, genetic variability, and UV radiation during human expansion.American journal of biological anthropology · 2023Review
- Methodological and Biological Factors Influencing Global DNA Methylation Results Measured by LINE-1 Pyrosequencing Assay in Colorectal Tissue and Liquid Biopsy Samples.International journal of molecular sciences · 2022Article
- MTHFR Knockdown Assists Cell Defense against Folate Depletion Induced Chromosome Segregation and Uracil Misincorporation in DNA.International journal of molecular sciences · 2021Article
- Folinate Supplementation Ameliorates Methotrexate Induced Mitochondrial Formate Depletion In Vitro and In Vivo.International journal of molecular sciences · 2021Article
- Tracing Metabolic Fate of Mitochondrial Glycine Cleavage System Derived Formate In Vitro and In Vivo.International journal of molecular sciences · 2020Article
- Investigating the methylation status ofMolecular biology research communications · 2019Article
- Association of Single Nucleotide Polymorphisms (SNPs) in Genes Encoding for Folate Metabolising Enzymes with Glioma and Meningioma in Indian PopulationAsian Pacific journal of cancer prevention : APJCP · 2018Article
- The MTHFR polymorphism affect the susceptibility of HCC and the prognosis of HCC liver transplantation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Article
- MTHFR gene variants and non-MALT lymphoma development in primary Sjogren's syndrome.Scientific reports · 2017Article
- Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in an Iranian Population.International journal of hematology-oncology and stem cell research · 2016Article
- Mthfr as a modifier of the retinal phenotype of Crb1(rd8/rd8) mice.Experimental eye research · 2016Article
- The association between RFC1 G80A polymorphism and cancer susceptibility: Evidence from 33 studies.Journal of Cancer · 2016Article
- Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility.Meta gene · 2015Review
- Lower serum folate is associated with development and invasiveness of gastric cancer.World journal of gastroenterology · 2014Article
- MTHFR C677T polymorphism, folate status and colon cancer risk in acromegalic patients.Pituitary · 2014Article
- Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes.Evolution, medicine, and public health · 2014Article
Corrections and comments
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Authors and funding
14 authors at 9 institutions in 4 countries.
Funding
Abstract
The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased risk of colon cancer although it may increase the risk of breast cancer. This polymorphism is associated with changes in intracellular folate cofactors, which may affect DNA methylation and synthesis via altered one-carbon transfer reactions. We investigated the effect of this mutation on DNA methylation and uracil misincorporation and its interaction with exogenous folate in further modulating these biomarkers of one-carbon transfer reactions in an in vitro model of the MTHFR 677T mutation in HCT116 colon and MDA-MB-435 breast adenocarcinoma cells. In HCT116 cells, the MTHFR 677T mutation was associated with significantly increased genomic DNA methylation when folate supply was adequate or high; however, in the setting of folate insufficiency, this mutation was associated with significantly decreased genomic DNA methylation. In contrast, in MDA-MB-435 cells, the MTHFR 677T mutation was associated with significantly decreased genomic DNA methylation when folate supply was adequate or high and with no effect when folate supply was low. The MTHFR 677T mutation was associated with a nonsignificant trend toward decreased and increased uracil misincorporation in HCT116 and MDA-MB-435 cells, respectively. Our data demonstrate for the first time a functional consequence of changes in intracellular folate cofactors resulting from the MTHFR 677T mutation in cells derived from the target organs of interest, thus providing a plausible cellular mechanism that may partly explain the site-specific modification of colon and breast cancer risks associated with the MTHFR C677T mutation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.