Journal
JOURNAL OF NUTRITION
Volume 137, Issue 9, Pages 2114-2120Publisher
AMER SOC NUTRITION-ASN
DOI: 10.1093/jn/137.9.2114
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Funding
- NCI NIH HHS [K05 CA100048, U54 CA100971] Funding Source: Medline
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Adequate folate availability is necessary to sustain normal DNA synthesis and normal patterns of DNA methylation and these features of DNA can be modified by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. This study investigated the effect of MTHFR C677T genotype and daily supplementation with 5 mg folic acid and 1.25 mg vitamin B-1 2 on uracil misincorporation into DNA and promoter methylation. Subjects (n = 86) with a history of colorectal adenoma and MTHFR CC or TT genotype were randomly assigned to receive folic acid plus vitamin B-1 2 or placebo for 6 mo. Uracil misincorporation and promoter methylation of 6 tumor suppressor and DNA repair genes were assessed in DNA from rectal biopsies at baseline and after the intervention. The biomarkers did not differ between the treated group and the placebo group after 6 mo compared with baseline. T e uracil concentration of DNA increased in the treated group (5.37 fmol/mu g DNA, P = 0.02), whereas it did not change in the placebo group (P= 0.42). The change from baseline of 4.01 fmol uracil/mu g DNA tended to differ between the groups (P= 0.16). An increase in promoter methylation tended to occur more often in the intervention group than in the placebo group (OR = 1.67, P = 0.08). This study suggests that supplementation with high doses of folic acid and vitamin B-1 2 may not favorably influence uracil incorporation and promoter methylation in subjects with previous colorectal adenomas. Because such alterations may potentially increase the risk of neoplastic transformation, more research is needed to fully define the consequences of these molecular alterations.
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