scholarly journals Association of Folate and Vitamins Involved in the 1-Carbon Cycle with Polymorphisms in the Methylenetetrahydrofolate Reductase Gene (MTHFR) and Global DNA Methylation in Patients with Colorectal Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1368 ◽  
Author(s):  
Ariana Ferrari ◽  
Giovana Tardin Torrezan ◽  
Dirce Maria Carraro ◽  
Samuel Aguiar Junior
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Carbon Cycle ◽  
Methylenetetrahydrofolate Reductase ◽  
Tumor Stage ◽  
Serum Folate ◽  
Global Dna Methylation ◽  
Mthfr Polymorphisms ◽  
Dietary Folate ◽  
Colon And Rectal Cancer

Folate, vitamin B2, vitamin B6, vitamin B12, choline, and betaine are nutrients involved in the 1-carbon cycle that can alter the levels of DNA methylation and influence genesis and/or tumor progression. Thus, the objective of this study was to evaluate the association of folate and vitamins involved in the 1-carbon cycle and MTHFR polymorphisms in global DNA methylation in patients with colorectal cancer gene. The study included 189 patients with colorectal adenocarcinoma answering a clinical evaluation questionnaire and the Food Frequency Questionnaire (FFQ) validated for patients with colon and rectal cancer. Blood samples were collected for evaluation of MTHFR gene polymorphisms in global DNA methylation in blood and in tumor. The values for serum folate were positively correlated with the equivalent total dietary folate (total DFE) (rho = 0.51, p = 0.03) and global DNA methylation (rho = 0.20, p = 0.03). Individuals aged over 61 years (p = 0.01) in clinicopathological staging III and IV (p = 0.01) and with + heterozygous mutated homozygous genotypes for the MTHFR A1298C gene had higher levels of global DNA methylation (p = 0.04). The association between dietary intake of folate, serum folate, and tumor stage were predictive of global DNA methylation in patients’ blood. The levels of serum folate, the dietary folate and the status of DNA methylation can influence clinicopathological staging.

scholarly journals Effects of Periconceptional Multivitamin Supplementation on Folate and Homocysteine Levels Depending on Genetic Variants of Methyltetrahydrofolate Reductase in Infertile Japanese Women

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1381
Author(s):  
Keiji Kuroda ◽  
Takashi Horikawa ◽  
Yoko Gekka ◽  
Azusa Moriyama ◽  
Kazuki Nakao ◽  
...  
Keyword(s):  
Folic Acid ◽  
Methylenetetrahydrofolate Reductase ◽  
Homocysteine Level ◽  
Folic Acid Supplementation ◽  
Serum Folate ◽  
Folate Level ◽  
Multivitamin Supplementation ◽  
Mthfr Polymorphisms ◽  
Mthfr Genotype ◽  
Multivitamin Supplements

Methylenetetrahydrofolate reductase (MTHFR) has various polymorphisms, and the effects of periconceptional folic acid supplementation for decreasing neural tube defects (NTDs) risk differ depending on the genotypes. This study analyzed the effectiveness of multivitamin supplementation on folate insufficiency and hyperhomocysteinemia, depending on MTHFR polymorphisms. Of 205 women, 72 (35.1%), 100 (48.8%) and 33 (16.1%) had MTHFR CC, CT and TT, respectively. Serum folate and homocysteine levels in women with homozygous mutant TT were significantly lower and higher, respectively, than those in women with CC and CT. In 54 women (26.3% of all women) with a risk of NTDs, multivitamin supplementation containing folic acid and vitamin D for one month increased folate level (5.8 ± 0.9 to 19.2 ± 4.0 ng/mL, p < 0.0001) and decreased the homocysteine level (8.2 ± 3.1 to 5.8 ± 0.8 nmol/mL, p < 0.0001) to minimize the risk of NTDs in all women, regardless of MTHFR genotype. Regardless of MTHFR genotype, multivitamin supplements could control folate and homocysteine levels. Tests for folate and homocysteine levels and optimal multivitamin supplementation in women with risk of NTDs one month or more before pregnancy should be recommended to women who are planning a pregnancy.

scholarly journals Folate metabolism modifies chromosomal damage induced by 1,3-butadiene: results from a match-up study in China and in vitro experiments

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Menglong Xiang ◽  
Zhi Wang ◽  
Peng Zou ◽  
Xi Ling ◽  
Guowei Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylenetetrahydrofolate Reductase ◽  
Micronucleus Assay ◽  
Folate Metabolism ◽  
Global Dna Methylation ◽  
Dependent Manner ◽  
Chromosomal Damage ◽  
Dna Hypomethylation ◽  
Exposed Workers ◽  
Tk6 Cells

Abstract Objectives To explore the role of folate metabolism in 1,3-Butadiene (BD)'s genotoxicity, we conducted a match-up study in BD-exposed workers in China to analyze the associations between the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and the chromosomal damage induced by BD exposure, and culture-based experiments in TK-6 cells to examine the global DNA methylation levels and chromosomal damage when exposed both to BD’s genotoxic metabolite, 1,2:3,4-diepoxybutane (DEB), and MTHFR’s direct catalytic product, 5-methyltetrahydrofolate (5-MTHF). Methods Cytokinesis block micronucleus assay (CBMN) was used to examine the chromosomal damage induced by BD or DEB. Poisson regression models were produced to quantify the relationship of chromosomal damage and genetic polymorphisms in the BD-exposed workers. Global DNA methylation levels in TK6 cells were examined using DNA Methylation Quantification Kit. Results We found that BD-exposed workers carrying MTHFR C677T CC (2.00 ± 2.00‰) (FR = 0.36, 95%CI: 0.20–0.67, P < 0.01) or MTHFR C677T CT (2.87 ± 1.98‰) (FR = 0.49, 95%CI: 0.32–0.77, P < 0.01) genotypes had significantly lower nuclear bud (NBUD) frequencies than those carrying genotype MTHFR 677 TT (5.33 ± 2.60‰), respectively. The results in TK6 cells showed that there was a significant increment in frequencies of micronucleus (MN), nucleoplasmic bridge (NPB) and nuclear bud (NBUD) with exposure to DEB at each 5-MTHF dose (ANOVA, P < 0.01). Additionally, there was a significant decrease in frequencies of MN, NPB and NBUD in DEB-exposed cultures with increasing concentration of 5-MTHF (ANOVA, P < 0.05). The levels of global DNA methylation were significantly decreased by DEB treatment in a dose-dependent manner within each 5-MTHF concentration in TK-6 cells (ANOVA, P < 0.01), and were significantly increased by 5-MTHF supplementation within each DEB concentration (ANOVA, P < 0.01). Conclusion We reported that folate metabolism could modify the association between BD exposure and chromosomal damage, and such effect may be partially mediated by DNA hypomethylation, and 5-MTHF supplementation could rescue it.

scholarly journals Association between Serum Vitamin B12 and Global DNA Methylation in Colorectal Cancer Patients

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3567 ◽  
Author(s):  
Hatim Boughanem ◽  
Pablo Hernandez-Alonso ◽  
Alberto Tinahones ◽  
Nancy Babio ◽  
Jordi Salas-Salvadó ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Vitamin B12 ◽  
Serum Vitamin ◽  
Global Dna Methylation ◽  
Inverse Association ◽  
Insulin Metabolism ◽  
High Vitamin ◽  
Line1 Methylation ◽  
Tumor Area

Vitamin B12 has been widely related to methionine metabolism, which is an essential component for biological methylation reactions, including DNA methylation. However, the relationship between vitamin B12 and DNA methylation is still controversial. In addition, there is increasing evidence for the association between vitamin B12 and the risk of colorectal cancer (CRC), although results of this association need to be assessed with caution. For this purpose, we hypothesized that serum vitamin B12 could be associated with global DNA methylation in the CRC context. To test this hypothesis, we studied the association between global DNA methylation through long interspersed nuclear element-1 (LINE1) in CRC patients under the 25th percentile of serum vitamin B12. We found that the high vitamin B12 group had low LINE1 methylation in both tumor area and peripheral blood mononuclear cells (PBMCs) than the low serum vitamin B12 group. LINE1 methylation levels were significantly lower in tumor area compared to the adjacent tumor-free area, only in the high vitamin B12 group. LINE1 methylation in visceral adipose tissue (VAT) and PBMCs were correlated with tumoral, inflammatory, and insulin metabolism markers. However, the interaction between LINE1 methylation and vitamin B12 levels was associated with neoadjuvant therapy in the regression analysis only in men, suggesting a beneficial relationship. In conclusion, our results reported an inverse association between DNA methylation and vitamin B12 in the CRC context, which suggests that vitamin B12 may be implicated in an epigenetic state or mediation in CRC.

scholarly journals Association between serum 25-hydroxyvitamin D and global DNA methylation in visceral adipose tissue from colorectal cancer patients

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Daniel Castellano-Castillo ◽  
Sonsoles Morcillo ◽  
Ana B. Crujeiras ◽  
Lidia Sánchez-Alcoholado ◽  
Mercedes Clemente-Postigo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Cancer Patients ◽  
Visceral Adipose Tissue ◽  
Global Dna Methylation ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Colorectal Cancer Patients ◽  
Visceral Adipose

Association of MTHFR C677T Variant Genotype with Serum Folate and Vit B12 in Iranian Patients with Colorectal Cancer or Adenomatous Polyps

2020 ◽  
Author(s):  
Mahla Ghorbani ◽  
Javad Baharara ◽  
Mohammad Amin Kerachian
Keyword(s):  
Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr C677t ◽  
Taqman Probe ◽  
Serum Folate ◽  
P Value ◽  
Vitamin B ◽  
Wild Type ◽  
Blood Samples ◽  
Significant Difference

Abstract Background: The incidence of colorectal cancer (CRC) has increased vigorously during the last decades in Iran and clinical studies suggest that moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) and essential folate dietary intake may reduce the risk of CRC.The aim of this study was to investigate the clinical significance of C677T polymorphism within MTHFR gene and its correlation with the serum folate and Vit B12 in Iranian population suffering from CRC.Methods: Blood samples were taken from 207 Iranian individuals (103 males and 104 females) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Besides, sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. Finally, the correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk were analyzed.Results: In the current study, the most percentage of the MTHFR polymorphisms in healthy individuals belongs to CC genotype (wild type). In patients with adenoma the percentage of CC and CT genotype were approximately similar, but surprisingly in adenocarcinoma the percentage of CC genotype (wild type) was the highest (approximately 50%), and the percentage of CT and TT genotypes were slightly similar. Our study revealed that there was no significant difference between the amount of folate and Vit B12 in case and control groups (p value >0.05).Conclusions: We concluded that there is an association between pivotal concentration of serum folate/vitamin B12 and CRC, and this association is altered by MTHFR C677T genotype.

scholarly journals Prognostic Values of EPDR1 Hypermethylation and Its Inhibitory Function on Tumor Invasion in Colorectal Cancer

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 393 ◽  
Author(s):  
Chun-Ho Chu ◽  
Shih-Ching Chang ◽  
Hsiu-Hua Wang ◽  
Shung-Haur Yang ◽  
Kuo-Chu Lai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tumor Stage ◽  
Small Gtpase ◽  
Normal Tissues ◽  
Inhibitory Function ◽  
New Perspective

Aberrant DNA methylation is a potential mechanism underlying the development of colorectal cancer (CRC). Thus, identification of prognostic DNA methylation markers and understanding the related molecular functions may offer a new perspective on CRC pathogenesis. To that end, we explored DNA methylation profile changes in CRC subtypes based on the microsatellite instability (MSI) status through genome-wide DNA methylation profiling analysis. Of 34 altered genes, three hypermethylated (epidermal growth factor, EGF; carbohydrate sulfotransferase 10, CHST10; ependymin related 1, EPDR1) and two hypomethylated (bone marrow stromal antigen 2, BST2; Rac family small GTPase 3, RAC3) candidates were further validated in CRC patients. Based on quantitative methylation-specific polymerase chain reaction (Q-MSP), EGF, CHST10 and EPDR1 showed higher hypermethylated levels in CRC tissues than those in adjacent normal tissues, whereas BST2 showed hypomethylation in CRC tissues relative to adjacent normal tissues. Additionally, among 75 CRC patients, hypermethylation of CHST10 and EPDR1 was significantly correlated with the MSI status and a better prognosis. Moreover, EPDR1 hypermethylation was significantly correlated with node negativity and a lower tumor stage as well as with mutations in B-Raf proto-oncogene serine/threonine kinase (BRAF) and human transforming growth factor beta receptor 2 (TGFβR2). Conversely, a negative correlation between the mRNA expression and methylation levels of EPDR1 in CRC tissues and cell lines was observed, revealing that DNA methylation has a crucial function in modulating EPDR1 expression in CRC cells. EPDR1 knockdown by a transient small interfering RNA significantly suppressed invasion by CRC cells, suggesting that decreased EPDR1 levels may attenuate CRC cell invasion. These results suggest that DNA methylation-mediated EPDR1 epigenetic silencing may play an important role in preventing CRC progression.

scholarly journals Hiwi Promotes the Proliferation of Colorectal Cancer Cells via Upregulating Global DNA Methylation

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lin Yang ◽  
Lei Bi ◽  
Qingwei Liu ◽  
Meng Zhao ◽  
Bin Cao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cell Lines ◽  
Adenovirus Vector ◽  
Global Dna Methylation ◽  
Cell Renewal ◽  
Western Blot Assay ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Ht 29

Hiwi is well known for its role in stem cell renewal, maintaining the resting stage, and downregulating cell cycle of stem cells via RNA silencing. And Hiwi overexpression has been recognized in several types of cancers. In the present study, we examined the Hiwi expression in colorectal cancer (CRC) specimens in both mRNA and protein levels via real-time quantitative PCR, western blot assay, and immunohistochemical staining. Then we explored the role of Hiwi in the cancer cell proliferation and in the DNA methylation in human CRC Caro-2 and HT-29 cell lines. Results demonstrated that both mRNA and protein levels of Hiwi were significantly higher in 38 CRC tissues than in 38 peritumor tissues. Moreover, the Hiwi overexpression with an adenovirus vector significantly promoted the proliferation of Caro-2 and HT-29 cells, associated with significant increase in the global DNA methylation levels. And the chemical inhibition of DNA methylation significantly restrained such proliferation promotion. In summary, we confirmed that Hiwi was overexpressed in CRC tissues and that the forced Hiwi overexpression promoted the proliferation and global DNA methylation of CRC cell lines. Our results imply for the first time that Hiwi promotes the proliferation of CRC cells via promoting global DNA methylation.

Sign in / Sign up

Export Citation Format

Share Document