Interventional study of high dose folic acid in gastric carcinogenesis in beagles

Xiao, Shu Dong; Meng, Xiangchuan; Shi, Yanhong; Hu, Yajun; Zhu, Shun-Shi; Wang, C W

doi:10.1136/gut.50.1.61

Cited by 45 publications

(35 citation statements)

References 24 publications

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“…18,19 Measurement of methylfolate concentrations in red blood cells may help to identify people at risk of venous thromboembolism. 20,21 The function of folic acid in DNA methylation and its maintenance Folate-derived one-carbon groups are essential for the de novo synthesis of nucleotide pyrimidines, thymidylate, and purines.…”

Section: Measurement Of Folic Acid Its Dietary Requirements and Dismentioning

confidence: 99%

Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis

Fang

Xiao

2003

Journal of Gastroenterology

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DNA methylation is the main epigenetic modification after replication in humans. DNA (cytosine-5)-methyltransferase (DNMT) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to C5 of cytosine within CpG dinucleotide sequences in the genomic DNA of higher eukaryotes. There is considerable evidence that aberrant DNA methylation plays an integral role in carcinogenesis. Folic acid or folate is crucial for normal DNA synthesis and can regulate DNA methylation, and through this, it affects cellular SAM levels. Folate deficiency results in DNA hypomethylation. Epidemiological studies have indicated that folic acid protects against gastrointestinal (GI) cancers. Methylene-tetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are the enzymes involved in folate metabolism and are thought to influence DNA methylation. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Two common MTHFR polymorphisms, 677CT (or 677TT) and A1298C, and an MS polymorphism, A-->G at 2756, have been identified. Most studies support an inverse association between folate status and the rate of colorectal adenomas and carcinomas. During human GI carcinogenesis, MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level, as well as aberrant methylation.

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Section: Measurement Of Folic Acid Its Dietary Requirements and Dismentioning

confidence: 99%

Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis

Fang

Xiao

2003

Journal of Gastroenterology

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“…Folate is one of the important constituents in fruits and vegetables, and low folate intake has been associated with an increased risk for a number of gastrointestinal cancers (7), including gastric cancer (8). Recently, two intervention studies provided strong evidence on the chemopreventive effect of folic acid on gastric cancer in both animal models (9) and human population (10).…”

mentioning

confidence: 99%

Polymorphisms of MTHFD, Plasma Homocysteine Levels, and Risk of Gastric Cancer in a High-Risk Chinese Population

Wang

Qiao

Chen

et al. 2007

Clinical Cancer Research

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Purpose: Accumulative evidence suggests that folate has a protective effect on gastric cancer.The methylenetetrahydrofolate dehydrogenase (MTHFD) plays an important role in folate and homocysteine metabolisms, and polymorphisms of MTHFD may result in disturbance of the folate-mediated homocysteine pathway. The aim of this study is to test the hypothesis that genetic variants of MTHFD and plasma homocysteine levels are associated with risk of gastric cancer and modulated by genotypes of methylenetetrahydrofolate reductase (MTHFR). Experimental Design: We genotyped G1958A and T401C in MTHFD and C677T in MTHFR and detected total plasma homocysteine (tHcy) levels in a case-control study of 589 gastric cancer cases and 635 cancer-free controls in a high-risk Chinese population. Results: The variant genotypes of MTHFD 1958AA and 401CC were associated with a significantly increased risk of gastric cancer [adjusted odds ratio (OR), 2.05; 95% confidence interval (95% CI), 1.34-3.13 for 1958AA; adjusted OR, 1.43; 95% CI, 1.14-1.80 for 401CC] compared with 1958GG/GA and 401TT/TC genotypes, respectively. Both of the effects were more evident in the subjects carrying MTHFR 677CT/TTgenotypes. The average tHcy level was significantly higher in gastric cancer cases than in controls (P < 0.01), and the upper quartile of tHcy (>13.6 Amol/L) was associated with an 82% significantly increased risk of gastric cancer, compared with the lowest quartile of tHcy (V8.0 Amol/L; adjusted OR, 1.82; 95% CI, 1.20-2.75). Conclusions: The strong associations between MTHFD variants and the plasma tHcy levels and gastric cancer risk suggest, for the first time, a possible gene-environment interaction between genetic variants of folate-metabolizing genes and high tHcy levels in gastric carcinogenesis.

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“…Only few animal studies have investigated this link. High folic acid supplementation was found to be protective against N -ethyl-N -nitrosoguanidine-induced GC in beagles (Xiao et al 2002 ). In a rodent model, folic acid supplementation was able to decrease mucosal infl ammation and dysplasia induced in hypergastrinemic mice infected with Helicobacter felis (Gonda et al 2012 ).…”

Section: Gastric Cancermentioning

confidence: 97%

One-Carbon Metabolism Nutrients and Epigenetics: A Mechanistic Link Between Aberrant One-Carbon Metabolism and Cancer Risk?

Masih

Plumptre

Kim

2014

Molecular Mechanisms and Physiology of Disease

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In relation to the genome, investigation of the epigenome is emerging as an equal, if not more infl uential factor in modulating human health and disease. Since epigenetic modifi cations are gradual in onset and potentially reversible, determining factors that modulate the epigenome is critical for possible preventive and therapeutic interventions. The development and progression of cancer is mechanistically linked to a number of epigenetic changes, including global DNA hypomethylation and genespecifi c CpG promoter DNA hypermethylation. Environmental factors, including diet, have been shown to affect cancer risk, via epigenetic and non-epigenetic mechanisms. In this regard, one-carbon nutrients are prototypic dietary factors that may modulate cancer risk via epigenetic mechanisms. This chapter will discuss the role of nutrients involved in one-carbon metabolism and their effect on cancer risk via epigenetic modifi cations with a particular focus on DNA methylation.

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Interventional study of high dose folic acid in gastric carcinogenesis in beagles

Cited by 45 publications

References 24 publications

Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis

Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis

Polymorphisms of MTHFD, Plasma Homocysteine Levels, and Risk of Gastric Cancer in a High-Risk Chinese Population

One-Carbon Metabolism Nutrients and Epigenetics: A Mechanistic Link Between Aberrant One-Carbon Metabolism and Cancer Risk?

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