The Effects of Alcohol on Folate Metabolism

Hillman, Robert W.; Steinberg, Stephen E.

doi:10.1146/annurev.me.33.020182.002021

Cited by 159 publications

(75 citation statements)

References 18 publications

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“…Additional dietary cofactors, such as methionine, alcohol, and vitamins B12 and B6 also influence methylation processes. Alcohol interferes with folate absorption and transport, resulting in potent acute and chronic effects on folate metabolism (Hillman and Steinberg, 1982). Animal and human studies have shown that 'methyl poor' diets (high alcohol-low methionine-low folate) are associated with 3-4-fold increases in the risk of both colorectal adenomas and cancer compared to 'methyl-rich' diets (low alcohol-high methionine-high folate) (Giovannucci, 2002).…”

Section: Folatementioning

confidence: 99%

Diet and cancer prevention

2004

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Dietary effects are presumed to underlie many of the large international differences in incidence seen for most cancers. Apart from alcohol and a few micronutrients, however, the role of specific nutritional factors remains illdefined. The evidence for a role of energy balance, physical inactivity, and obesity has strengthened, while for dietary fat it has weakened. Phytochemicals such as folate, lycopene and flavonoids are still the subject of active research. As the mechanisms underlying human carcinogenesis are better understood, dietary research will focus increasingly on intermediate markers such as the insulin-like growth factors and potentially carcinogenic metabolites.

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Section: Folatementioning

confidence: 99%

Diet and cancer prevention

2004

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“…MTHFR regulates the synthesis of 5-methyl-tetrahydrofolate by catalyzing the irreversible conversion from 5,10-methylene-tetrahydrofolate to 5-methyl-tetrahydrofolate. Importantly, alcohol consumption interferes with folate metabolism (6), and decreases the levels of serum folate (7), of which 5-methyl-tetrahydrofolate is the predominant component.…”

Section: Introductionmentioning

confidence: 99%

Methionine Synthase A2756G Polymorphism Interacts with Alcohol and Folate Intake to Influence the Risk of Colorectal Adenoma

Yamaji

Iwasaki²,

Sasazuki³

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Genomic DNA hypomethylation has been associated with colorectal carcinogenesis. Methionine synthase A2756G (MTR A2756G) is a common nonsynonymous polymorphism in the gene that encodes methionine synthase, a key enzyme in the pathway leading to DNA methylation. Several studies, but not all, have reported relatively lower plasma homocysteine among individuals with the AG or GG genotype. Meanwhile, higher plasma homocysteine was associated with genomic DNA hypomethylation in healthy volunteers. We therefore hypothesized that minor allele carriers possess a decreased risk of colorectal adenoma, and examined this hypothesis in a case-control study of colorectal adenoma in Japan involving 723 cases and 670 controls. An unconditional logistic regression model was used to estimate odds ratios (OR) and their 95% confidence intervals (95% CI) for colorectal adenoma after adjustment for potential confounders. Despite the lack of an overall association, we observed a significant interaction between MTR A2756G and alcohol intake (P for interaction = 0.007). Compared with never drinkers with the AA genotype, never drinkers with the AG or GG genotype exhibited a significantly decreased risk (OR, 0.56; 95% CI, 0.34-0.90) whereas heavy drinkers with the same genotypes showed a substantially increased risk (OR, 1.90; 95% CI, 1.04-3.46). In addition, a marginally significant interaction was observed with folate intake (P for interaction = 0.07). The G allele may confer protection against colorectal adenoma in the presence of a considerably good folate status. Our findings add to increasing evidence that DNA methylation plays an important role even at an early stage of colorectal carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2009;18(1):267 -74)

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“…Alcohol antagonizes folate and disrupts many aspects of normal folate transport and metabolism by preventing the release of folate from hepatocytes (28). Moderate-to-high alcohol intake interferes with folate bioavailability (29).…”

Section: Introductionmentioning

confidence: 99%

DNA Methyltransferase and Alcohol Dehydrogenase: Gene-Nutrient Interactions in Relation to Risk of Colorectal Polyps

Jung¹,

Poole²,

Bigler³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Disturbances in DNA methylation are a characteristic of colorectal carcinogenesis. Folate-mediated one-carbon metabolism is essential for providing one-carbon groups for DNA methylation via DNA methyltransferases (DNMTs). Alcohol, a folate antagonist, could adversely affect one-carbon metabolism. In a casecontrol study of colorectal polyps, we evaluated three single nucleotide polymorphisms (À149C>T, À283T>C, À579G>T) in the promoter region of the DNMT3b gene, and a functional polymorphism in the coding region of the alcohol dehydrogenase ADH1C gene, ADH1C *2. Cases had a first diagnosis of colorectal adenomatous (n = 530) or hyperplastic (n = 202) polyps at the time of colonoscopy, whereas controls were polyp-free (n = 649). Multivariate logistic regression analysis was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI). There were no significant main associations between the DNMT3b or ADH1C polymorphisms and polyp risk. However, DNMT3b À149TT was associated with an increase in adenoma risk among individuals with low folate and methionine intake (OR, 2.00; 95% CI, 1.06-3.78, P interaction = 0.10). The ADH1C *2/*2 genotype was associated with a possibly elevated risk for adenomatous polyps among individuals who consumed >26 g of alcohol/d (OR, 1.95; 95% CI, 0.60-6.30), whereas individuals who were wildtype for ADH1C were not at increased risk of adenoma (P interaction = 0.01). These gene-diet interactions suggest that polymorphisms relevant to DNA methylation or alcohol metabolism may play a role in colorectal carcinogenesis in conjunction with a high-risk diet.

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The Effects of Alcohol on Folate Metabolism

Cited by 159 publications

References 18 publications

Diet and cancer prevention

Diet and cancer prevention

Methionine Synthase A2756G Polymorphism Interacts with Alcohol and Folate Intake to Influence the Risk of Colorectal Adenoma

DNA Methyltransferase and Alcohol Dehydrogenase: Gene-Nutrient Interactions in Relation to Risk of Colorectal Polyps

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