Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake

Cravo, Marília; Pinto, Armando; Chaves, Paula; Cruz, Jordão Aires Lustosa da; Lage, Pedro; Leitão, C. Nobre; Mira, F. Costa

doi:10.1016/s0261-5614(98)80304-x

Cited by 109 publications

(88 citation statements)

References 30 publications

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“…Folate deficiency in rats has been shown to decrease SAM in several tissues, but with little effect on DNA methylation (Sohn et al, 2003). Conversely, folate supplementation has been reported to decrease global DNA hypomethylation in seven of 20 patients with resected colonic adenomas (Cravo et al, 1998). In our healthy population, folate supplementation increased whole blood SAM but did not alter lymphocyte global DNA methylation.…”

Section: Discussionmentioning

confidence: 60%

Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers

Basten

Duthie²,

Pirie³

et al. 2006

Br J Cancer

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We have previously reported that supplementation with folic acid (1.2 mg day À1 for 12 week) elicited a significant improvement in the folate status of 61 healthy volunteers. We have examined effects of this supplement on markers of genomic stability. Little is known about the effect of folate supplementation on DNA stability in a cohort, which is not folate deficient. Preintervention, there was a significant inverse association between uracil misincorporation in lymphocyte DNA and red cell folate (Po0.05). In contrast, there were no associations between folate status and DNA strand breakage, global DNA methylation or DNA base excision repair (measured as the capacity of the lymphocyte extract to repair 8-oxoGua ex vivo). Folate supplementation elicited a significant reduction in uracil misincorporation (Po0.05), while DNA strand breakage and global DNA methylation remained unchanged. Increasing folate status significantly decreased the base excision repair capacity in those volunteers with the lowest preintervention folate status (Po0.05). Uracil misincorporation was more sensitive to changes in folate status than other measures of DNA stability and therefore could be considered a specific and functional marker of folate status, which may also be relevant to cancer risk in healthy people. Epidemiological studies have consistently revealed an association between the consumption of fruit and vegetables and reduced incidence of cancers at various sites. Although the active dietary components have not been identified, folate has received a significant amount of attention. A relative deficiency of folate has been associated with precancerous lesions or cancer of the breast, large bowel, cervix, oesophagus, lung and pancreas (Jaskiewicz et

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Section: Discussionmentioning

confidence: 60%

Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers

Basten

Duthie²,

Pirie³

et al. 2006

Br J Cancer

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“…To date, there has been conflicting evidence about the extent of global and repeat element hypomethylation in otherwise normal colorectal mucosa of patients with cancer. Regional or colon-wide hypomethylation has been reported in the macroscopically normal mucosa of colorectal cancer patients (19,38), raising the possibility of a "field defect" that may predispose to tumor development. In contrast, others have found no significant difference in global (39) or repeat element methylation (40) in this setting, although folic acid supplementation or short-term depletion (sufficient to modify total colonic folate concentration) do not alter colonic global (26) or LINE-1 methylation (41).…”

Section: Discussionmentioning

confidence: 99%

Relative Distribution of Folate Species Is Associated with Global DNA Methylation in Human Colorectal Mucosa

Liu

Hesson

Meagher

et al. 2012

Cancer Prevention Research

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Folate exists as functionally diverse species within cells. Although folate deficiency may contribute to DNA hypomethylation in colorectal cancer, findings on the association between total folate concentration and global DNA methylation have been inconsistent. This study determined global, LINE-1, and Alu DNA methylation in blood and colon of healthy and colorectal cancer patients and their relationship to folate distribution. Blood and normal mucosa from 112 colorectal cancer patients and 114 healthy people were analyzed for global DNA methylation and folate species distribution using liquid chromatography tandem mass spectrometry. Repeat element methylation was determined using end-specific PCR. Colorectal mucosa had lower global and repeat element DNA methylation compared with peripheral blood (P < 0.0001). After adjusting for age, sex and smoking history, global but not repeat element methylation was marginally higher in normal mucosa from colorectal cancer patients compared with healthy individuals. Colorectal mucosa from colorectal cancer subjects had lower 5-methyltetrahydrofolate and higher tetrahydrofolate and formyltetrahydrofolate levels than blood from the same individual. Blood folate levels should not be used as a surrogate for the levels in colorectal mucosa because there are marked differences in folate species distribution between the two tissues. Similarly, repeat element methylation is not a good surrogate measure of global DNA methylation in both blood and colonic mucosa. There was no evidence that mucosal global DNA methylation or folate distribution was related to the presence of cancer per se, suggesting that if abnormalities exist, they are confined to individual cells rather than the entire colon. Cancer Prev Res; 5(7);

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“…Folate deficiency has not been shown unequivocally to induce genomic or site-specific DNA hypomethylation but is still considered as a possible mechanism. Cravo et al 53,54 observed that folate supplementation significantly reversed genomic DNA hypomethylation of the colonic mucosa. Kim et al 55 reported that DNA methylation underwent improvement with folate supplementation.…”

Section: Discussionmentioning

confidence: 99%

Intake of dietary folate vitamers and risk of colorectal carcinoma

Konings

Goldbohm

Brants

et al. 2002

Cancer

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BACKGROUNDSeveral studies have reported inverse associations between folate intake and colorectal carcinoma risk. Few were prospective studies and none evaluated the association between the intake of individual folate vitamers and colorectal carcinoma risk.METHODSThe aim of the current study was to investigate the relationship between dietary folate intake and the risk of colorectal carcinoma in a large prospective cohort study in The Netherlands comprising 120,852 men and women aged 55–69 years. After 7.3 years of follow‐up, 760 colon and 411 rectal carcinoma cases were available for analysis. Data processing and analysis used the case–cohort approach. A new Dutch database was used to estimate intakes of total and individual folate vitamers.RESULTSAnalyses adjusted for age, energy intake, family history of colorectal carcinoma, alcohol, vitamin C, iron, and dietary fiber intake yielded an inverse association between colon carcinoma risk and total dietary folate intake (rate ratio [RR]highest vs. lowest quintile, men: 0.73; 95% confidence interval [CI], 0.46–1.17, P trend = 0.03; women: 0.68; 95% CI, 0.39–1.20, P trend = 0.18). An inverse association between rectal carcinoma and total dietary folate intake was found only among men (RR highest vs. lowest quintile, men: 0.66; 95% CI, 0.35–1.21, P trend = 0.03). Analyses showed no clear difference in colorectal carcinoma risk associated with intake of different folate vitamers.CONCLUSIONSDietary folate intake was related inversely to colon and male rectal carcinoma risk. Cancer 2002;95:1421–33. © 2002 American Cancer Society.DOI 10.1002/cncr.10866

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Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake

Cited by 109 publications

References 30 publications

Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers

Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers

Relative Distribution of Folate Species Is Associated with Global DNA Methylation in Human Colorectal Mucosa

Intake of dietary folate vitamers and risk of colorectal carcinoma

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