Methylenetetrahydrofolate Reductase C677T is Not Associated with Expression of Pyrimidine Metabolic Enzyme Genes in Colorectal Cancer

2006 ◽  
Vol 34 (3) ◽  
pp. 307-315 ◽  
Author(s):  
R Takeda ◽  
T Kamano ◽  
K Sakamoto ◽  
M Sugano ◽  
S Hosoda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Dihydropyrimidine Dehydrogenase ◽  
Mrna Level ◽  
Mthfr C677t ◽  
Normal Mucosa ◽  
Metabolic Enzyme ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Normal Tissues

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may influence the chemosensitivity of colorectal cancers to fluorouracil (5-FU) by increasing intracellular 5, 10-methylenetetrahydrofolate. The effect of this polymorphism on the expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in colorectal cancer was investigated. The MTHFR C677T polymorphism was analysed and TS, DPD, OPRT and TP mRNA expression was measured in tumour and adjacent normal mucosal tissue. In all patients, the genotypes of the tumour and normal tissues were identical. No differences were found in the expression of TS, DPD or TP mRNA by genotype in either tumour or normal tissue. Although the OPRT mRNA level in tumour tissue was not associated with the genotype, normal mucosa with the TT genotype showed a significantly higher OPRT mRNA level than mucosa with other genotypes. The MTHFR C667T polymorphism is not associated with intratumoural expression of TS, DPD, OPRT or TP.

scholarly journals Methylenetetrahydrofolate reductase C677T polymorphism and colorectal cancer susceptibility: a meta-analysis

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Lingyan Xu ◽  
Zhiqiang Qin ◽  
Feng Wang ◽  
Shuhui Si ◽  
Lele Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Publication Bias ◽  
Methylenetetrahydrofolate Reductase ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
Mthfr C677t ◽  
Control Group ◽  
C677t Polymorphism ◽  
Case Control Studies ◽  
Mthfr C677t Polymorphism

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and colorectal cancer (CRC) susceptibility has been researched in numerous studies. However, the results of these studies were controversial. Therefore, the objective of this meta-analysis was to offer a more convincible conclusion about such association with more included studies. Eligible studies published till May 1, 2017 were searched from PubMed, Embase, Web of Science, and CNKI database about such association. Pooled odds ratios (ORs) together with 95% confidence intervals (CIs) were calculated to evaluate such association. And the Begg’s funnel plot and Egger’s test were applied to assess the publication bias. This meta-analysis contained 37049 cases and 52444 controls from 87 publications with 91 eligible case–control studies. Because of lack of data for a particular genotype in several studies, all the included studies were analysed barely in the dominant model. Originally, there was no association between MTHFR C677T polymorphism and CRC susceptibility (OR =0.99, 95% CI =0.94–1.05). After excluding 13 studies according to their heterogeneity and publication bias, rs1801133 polymorphism was found to reduce the risks of CRC significantly (OR =0.96, 95% CI =0.94–0.99). In the subgroup analysis of ethnicity, there was a significant association in Asians (OR =0.94, 95% CI =0.89–1.00). Furthermore, when stratified by the source of controls and genotyping methods, the positive results were observed in population-based control group (OR =0.97, 95% CI =0.93–1.00) and PCR-restriction fragment length polymorphism (PCR-RFLP) method (OR =0.95, 95% CI =0.91–0.99. The results of the meta-analysis suggested that MTHFR C677T polymorphism was associated with CRC susceptibility, especially in Asian population.

scholarly journals Methylenetetrahydrofolate reductase C677T polymorphism and toxicity to 5-FU-based chemotherapy in colorectal cancer

2020 ◽  
Vol 19 (1) ◽  
pp. 209-213
Author(s):  
Yong-lian Zhang ◽  
Xiong-wei Xie
Keyword(s):  
Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Direct Sequencing ◽  
Skin Toxicity ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Mthfr Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
C677t Mutation ◽  
Hematopoietic Toxicity

Purpose: To investigate the toxicity of methylenetetrahydrofolate reductase (MTHFR) polymorphism in colorectal cancer patients treated with 5-fluorouracil (5-FU).Methods: A total of 105 patients with colorectal cancer who underwent 5-FU therapy were included in this study. MTHFR C677T polymorphisms were determined using direct sequencing. Physical examination and the results of blood and urine tests were used to evaluate the toxicities, including gastrointestinal toxicity, hematopoietic toxicity, hair-skin toxicity and hand-foot syndrome.Results: In 90.5 % of all patients, 5-FU toxicity was observed. With regard to MTHFR C677T mutation, 45.7 % heterozygote mutants and 19.0 % homozygote mutants were observed. MTHFR C677T polymorphism was statistically related to 5-FU toxicity (p = 0.000). In addition, MTHFR C677T mutation was closely related to hematopoietic toxicity (p = 0.005).Conclusion: MTHFR C677T can be used for the prediction of 5-FU toxicity, and can also predict hematopoietic toxicity in patients with colorectal cancer. Keywords: MTHFR genes, Polymorphism, Colorectal cancer, Biomarker, Toxicity

scholarly journals Effect of riboflavin supplementation on blood pressure and possible effect modification by the MTHFR C677T polymorphism: a randomised trial in rural Gambia

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1034
Author(s):  
Modou Jobe ◽  
Mary Ward ◽  
Bakary Sonko ◽  
Abdul Khalie Muhammad ◽  
Ebrima Danso ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Large Scale ◽  
Methylenetetrahydrofolate Reductase ◽  
Controlled Trial ◽  
Randomised Trial ◽  
Mthfr C677t ◽  
C677t Polymorphism ◽  
Phenotypic Effect ◽  
Riboflavin Deficiency ◽  
Mthfr C677t Polymorphism

Introduction: Emerging evidence links a functional polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene (rs1801133) with hypertension in adults. This variant reduces the affinity of MTHFR for its cofactor flavin-adenine dinucleotide (FAD) which is derived from riboflavin. Previous work has demonstrated a blood pressure (BP)-lowering effect of riboflavin in Irish adults with the MTHFR 677TT variant. We hypothesize that the almost-universal severe riboflavin deficiency seen in rural Gambia mimics the BP phenotypic effect of the TT variant and exacerbate the effect of the CT variant. We will test this in a randomised, placebo-controlled trial, whether intervention with riboflavin can decrease BP in adults in rural Gambia. Methods: This is a phase 2 recall-by-genotype randomised single-blind placebo-controlled riboflavin supplementation trial. We will use the Keneba biobank to recruit approximately 102 individuals aged between 18-70, previously genotyped for the MTHFR C677T polymorphism and identified as carrying the T allele; these individuals will be age- and sex-matched to a similar number of homozygotes for the C allele. The participants will be randomised to a 16-week supplementation trial of 5 mg/day riboflavin or placebo, supplied every 14 days. The primary outcome, BP, will be measured at baseline and at weeks 8 and 16. Blood samples, collected at baseline and week 16, will be analysed for riboflavin, homocysteine, red cell folate, cobalamin (vitamin B12) and pyridoxine (vitamin B6). Discussion: The study will evaluate the role of riboflavin supplementation in BP control within a population with high levels of riboflavin deficiency and will test a possible gene-nutrient interaction with the MTHFR C677T polymorphism. If improvements in BP are observed in this study, and proven in subsequent large-scale interventions, riboflavin could offer a cost-effective, safe and accessible option for the  prevention and control of hypertension in this population. Trial registration: ClinicalTrials.gov Identifier NCT03151096. Registered on 12 May 2017.

scholarly journals MTHFR Gene Polymorphism and Age of Onset of Schizophrenia and Bipolar Disorder

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed A. El-Hadidy ◽  
Hanaa M. Abdeen ◽  
Sherin M. Abd El-Aziz ◽  
Mohammad Al-Harrass
Keyword(s):  
Bipolar Disorder ◽  
Healthy Subjects ◽  
Methylenetetrahydrofolate Reductase ◽  
Age Of Onset ◽  
Age At Onset ◽  
Mthfr C677t ◽  
Control Group ◽  
C677t Polymorphism ◽  
Mthfr C677t Polymorphism ◽  
Mthfr Gene Polymorphism

Objective. Several studies with contradictory results from different cultures about association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in schizophrenia and bipolar disorders. Little is known about this association in Arab culture and Egypt. So the present study aimed to assess the association of MTHFR C677T polymorphism in bipolar disorder (BD) and schizophrenia in comparison to control group. The association between MTHFR C677T polymorphism and the age at onset in schizophrenia or BD was also studied.Methods. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were used to examine the genotype and allele frequencies of MTHFR C677T polymorphism in 149 healthy subjects and 134 bipolar and 103 schizophrenia patients.Results. In BD and schizophrenia, there was a higher prevalence of MTHFR C677T polymorphism than healthy subjects. Earlier age at onset was found in patients with BD, carrying one copy of the T allele or CT genotypes but not in patients with schizophrenia.Conclusion. The present findings suggest that the MTHFR C677T polymorphisms are likely to be associated with the risk of developing BD and schizophrenia and influence the age at onset of BD but not the age at onset of schizophrenia.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Mrna Level ◽  
Normal Mucosa ◽  
Tnm Stage ◽  
Expression Levels ◽  
Normal Tissues

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

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