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TitleFolic acid and vitamin B-12 supplementation does not favorably influence uracil incorporation and promoter methylation in rectal mucosa DNA of subjects with previous colorectal adenomas
Publication TypeJournal Article
Year of Publication2007
Authorsvan den Donk M, Pellis L, Crott JW, van Engeland M, Friederich P, Nagengast FM, van Bergeijk JD, de Boer SY, Mason JB, Kok FJ, Keijer J, Kampman E
JournalThe Journal of Nutrition
Keywords80 and over, Adolescent, Adult, Aged, Colorectal Neoplasms, Erythrocytes, Female, Folic Acid, Genetic, Genotype, Homocysteine, Humans, Intestinal Mucosa, Male, Middle Aged, Oxidoreductases Acting on {CH-NH} Group Donors, Promoter Regions, Uracil, Vitamin B 12, {DNA} Methylation

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-12 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-12 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. The uracil concentration of {DNA} increased in the treated group (5.37 fmol/microg {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/microg {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-12 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.