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.

Ariana Ferrari,Giovana Tardin Torrezan,Samuel Aguiar Junior,Dirce Maria Carraro

doi:10.3390/nu11061368

Ariana Ferrari, Giovana Tardin Torrezan + Show 2 more

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https://doi.org/10.3390/nu11061368

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Journal: Nutrients	Publication Date: Jun 18, 2019
Citations: 15	License type: CC BY 4.0

Affiliation: Centro Universitário Cesumar, AC Camargo Hospital

Abstract

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.

Highlights

Epigenetics is defined as inherited changes in gene expression, but without altering the base sequence of deoxyribonucleic acid (DNA), and may be reversible, unlike genetic alterations
As a vitamin involved in multiple biochemical processes, folate has been studied as an important modulator of carcinogenesis [24,25,26]
Folic acid is an essential nutrient for the 1-carbon cycle, which at one time participates in the synthesis of nucleotides and methylation reactions in the human organism [27]

Summary

Introduction

Epigenetics is defined as inherited changes in gene expression, but without altering the base sequence of deoxyribonucleic acid (DNA), and may be reversible, unlike genetic alterations. The most studied epigenetic mechanisms are DNA methylation, histone modifications, and the action of non-coding ribonucleic acids (RNAs) [1]. Methylation consists of the covalent addition of a methyl carbon group at the 5-position of the pyrimidine ring of the cytosine nucleotide of DNA, which usually precedes a guanine (CG dinucleotides) [2]. DNA methyltransferase enzymes (DNMTs) are essential for this reaction and results in the formation of 5-methylcytosine, a methylated form of cytosine [3]. This epigenetic event is essential for gene regulation.

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