ArticlePloS one2017
One-carbon genetic variants and the role of MTHFD1 1958G>A in liver and colon cancer risk according to global DNA methylation.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.The British journal of dermatology · 2020Pooled it
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- Low-Penetrance Susceptibility Variants in Colorectal Cancer-Current Outlook in the Field.International journal of molecular sciences · 2024Review
- Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis.iScience · 2024Article
- The Mediating Effect of the Choline-to-Betaine Ratio on the Association BetweenCurrent developments in nutrition · 2024Article
- Association Between Multiple Single Nucleotide Polymorphisms in Folate Metabolism Pathway and Breast Cancer Risk in Georgian Women: A Case-Control Study.Clinical Medicine Insights. Oncology · 2024Article
- Common Variants in One-Carbon Metabolism Genes (International journal of molecular sciences · 2023Article
- The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- DNA methylation in cell plasticity and malignant transformation in liver diseases.Pharmacology & therapeutics · 2023Review
- Article
- MTHFD1L, A Folate Cycle Enzyme, Is Involved in Progression of Colorectal Cancer.Translational oncology · 2019Article
- Methylenetetrahydrofolate Dehydrogenase 1 (MTHFD1) is Underexpressed in Clear Cell Renal Cell Carcinoma Tissue and Transfection and Overexpression in Caki-1 Cells Inhibits Cell Proliferation and Increases Apoptosis.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Methylenetetrahydrofolate Dehydrogenase 1 Silencing Expedites the Apoptosis of Non-Small Cell Lung Cancer Cells via Modulating DNA Methylation.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Sex Differences in Genetic Associations With Longevity.JAMA network open · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several polymorphic gene variants within one-carbon metabolism, an essential pathway for nucleotide synthesis and methylation reactions, are related to cancer risk. An aberrant DNA methylation is a common feature in cancer but whether the link between one-carbon metabolism variants and cancer occurs through an altered DNA methylation is yet unclear. Aims of the study were to evaluate the frequency of one-carbon metabolism gene variants in hepatocellular-carcinoma, cholangiocarcinoma and colon cancer, and their relationship to cancer risk together with global DNA methylation status. Genotyping for BHMT 716A>G, DHFR 19bp ins/del, MTHFD1 1958G>A, MTHFR 677C>T, MTR 2756A>G, MTRR 66A>G, RFC1 80G>A, SHMT1 1420C>T, TCII 776C>G and TS 2rpt-3rpt was performed in 102 cancer patients and 363 cancer-free subjects. Methylcytosine (mCyt) content was measured by LC/MS/MS in peripheral blood mononuclear cells (PBMCs) DNA. The MTHFD1 1958AA genotype was significantly less frequent among cancer patients as compared to controls (p = 0.007) and related to 63% reduction of overall cancer risk (p = 0.003) and 75% of colon cancer risk (p = 0.006). When considering PBMCs mCyt content, carriers of the MTHFD1 1958GG genotype showed a lower DNA methylation as compared to carriers of the A allele (p = 0.048). No differences were highlighted by evaluating a possible relationship between the other polymorphisms analyzed with cancer risk and DNA methylation. The MTHFD1 1958AA genotype is linked to a significantly reduced cancer risk. The 1958GG genotype is associated to PBMCs DNA hypomethylation as compared to the A allele carriership that may exert a protective effect for cancer risk by preserving from DNA hypomethylation.
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