ArticleMolecular medicine (Cambridge, Mass.)
MTHFR, MTR, and MTRR polymorphisms in relation to p16INK4A hypermethylation in mucosa of patients with colorectal cancer.
Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 4 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 4 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Meta Analysis of Methylenetetrahydrofolate Reductase (MTHFR) C677T polymorphism and its association with folate and colorectal cancer.BMC cancer · 2025Pooled it
- Unveiling the link: Evaluating MTHFR gene polymorphisms and colorectal cancer risk through meta-analysis.PloS one · 2025Pooled it
- Prognostic DNA methylation markers for sporadic colorectal cancer: a systematic review.Clinical epigenetics · 2018Pooled it
- Pooled it
- IncreasedMolecular & cellular oncology · 2025Article
- Epigenetic differences in the tumor suppressor genesInnovative surgical sciences · 2024Article
- Interactions between vitamin B2, the MTRR rs1801394 and MTR rs1805087 genetic polymorphisms, and colorectal cancer risk in a Korean population.Epidemiology and health · 2024Article
- Review
- Folate metabolism genetic polymorphisms and meningioma and glioma susceptibility in adults.Oncotarget · 2017Article
- Serum folate concentration and the incidence of lung cancer.PloS one · 2017Article
- Association ofJournal of Cancer · 2017Article
- Major Polymorphisms of Genes Involved in Homocysteine Metabolism in Malaria Patients in Ouagadougou, Burkina Faso.Malaria research and treatment · 2017Article
- Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker.International journal of molecular sciences · 2015Article
- Genetic variations in the one-carbon metabolism pathway genes and susceptibility to hepatocellular carcinoma risk: a case-control study.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity?Immunologic research · 2014Review
- Article
- Redox regulation of the epigenetic landscape in cancer: a role for metabolic reprogramming in remodeling the epigenome.Free radical biology & medicine · 2012Review
- Article
- Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2011Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We recently analyzed the hypermethylation status of the p16INK4a (p16) gene promoter in normal-appearing mucosa obtained from patients with colorectal cancer. Hypermethylation of p16 was associated with reduced survival of these patients. In the present study, germ line polymorphisms in the folate- and methyl-associated genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR), were analyzed in the same patient cohort to find a possible link between these genetic variants and p16 hypermethylation. Genomic DNA was extracted from blood of patients (n = 181) and controls (n = 300). Genotype analyses were run on an ABI PRISM(®) 7900HT sequence-detection system (Applied Biosystems), using real-time polymerase chain reaction and TaqMan chemistry. The results showed that the genotype distributions of the patient and control groups were similar. No significant differences in cancer-specific or disease-free survival of stage I-III patients according to polymorphic variants were detected, nor were any differences in cancer-specific or disease-free survival detected when patients were subgrouped according to the MTHFR or MTR genotype groups and dichotomized by p16 hypermethylation status in mucosa. However, patients with the MTRR 66 AA/AG genotypes were found to have a significantly worse cancer-specific survival when the mucosa were positive, compared with negative, for p16 hypermethylation (hazard ratio 2.7; 95% confidence interval 1.2-6.4; P = 0.023). In contrast, there was no difference in survival among patients with the MTRR 66 GG genotype stratified by p16 hypermethylation status. These results indicate a relationship between genetic germ-line variants of the MTRR gene and p16 hypermethylation in mucosa, which may affect the clinical outcome of patients with colorectal cancer.
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