Association of MTHFR C677T variant genotype with serum folate and Vit B12 in Iranian patients with colorectal cancer or adenomatous polyps.

BACKGROUND: The incidence of colorectal cancer (CRC) has increased during recent years in Iran and other developing countries. Clinical studies suggest that essential folate dietary intake and moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) may protect and reduce the risk of CRC. The present study aimed to investigate the clinical significance of C677T polymorphism within the MTHFR gene and its correlation with the serum folate and Vit B12 in the Iranian population suffering from CRC. METHODS: Blood samples were taken from 1017 Iranian individuals (517 cases and 500 controls) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. The correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk was analyzed. RESULTS: In the current study, we found the frequency of three different genotypes of MTHFR polymorphism in the Iranian population i.e., CC, CT, and TT, to be 51.31, 26.73, 21.96 and 61, 32.2, 6.8 in case and control groups, respectively. The homozygote genotype of MTHFR rs1801133 polymorphism is associated with an increased risk of CRC by 3.68, 1.42, and 3.74-fold in codominant, dominant, and recessive models respectively (p value < 0.01). Our study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups (p value > 0.05). CONCLUSIONS: This study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups. Furthermore, our results demonstrated a higher risk association for 677TT and 677TT + C677T genotypes of MTHFR compared with 677CC carriers among CRC patients.

Aberrantly methylated-differentially genes and pathways among Iranian patients with colorectal cancer.

BACKGROUND: Methylation plays an important role in colorectal cancer (CRC) pathogenesis. The goal of this study was to identify aberrantly differentially methylated genes (DMGs) and pathways through bioinformatics analysis among Iranian CRC patients using Methylation Next Generation Sequencing. METHODS: This study has integrated results of SureSelectXT Methyl-Seq Target with the potential key candidate genes and pathways in CRC. Six CRC and six samples of normal colon were integrated and deeply analyzed. In addition to this gene methylation profiling, several other gene methylation profiling datasets were obtained from Gene Expression Omnibus (GEO) and TCGA datasets. DMGs were sorted and candidate genes and enrichment pathways were analyzed. DMGs-associated protein-protein interaction network (PPI) was constructed based on the STRING online database. RESULTS: Totally, 320 genes were detected as common genes between our patients and selected GEO and TCGA datasets from the Agilent SureSelect analysis with selecting criteria of p-value < 0.05 and FC ≥ 1.5. DMGs were identified from hyper-DMGs PPI network complex and 10 KEGG pathways were identified. The most important modules were extracted from MCODE, as most of the corresponding genes were involved in cellular process and protein binding. CONCLUSIONS: Hub genes including WNT2, SFRP2, ZNF726 and BMP2 were suggested as potentially diagnostic and therapeutic targets for CRC.

Could high serum folate be associated with adverse effects?

Folate is an important water-soluble vitamin that is presented naturally in foods in particular vegetables, fruits, and whole grains. To which extent is this vitamin needed in our daily regimen is not fully known. Several studies have indicated that many complications, such as megaloblastic anemia, cardiovascular disease, neural tube defects, and numerous cancers, occur in humans when the body becomes deficient in folic acid. On the other hand, a few studies have shown thier concerns regarding the supplementation of folic acid, resulting in the development of existing tumors and alteration of normal patterns of DNA methylation. Although there is no clear evidence of aberrant DNA methylation and gene expression changes in response to "high" levels of folate or folic acid intake, there are still some concerns. Therefore, its adverse effects especially on fetus and later stages of life should be carefully investigated.