title: Folic 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.
abstract: 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.
authors: Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, The Netherlands.
authors: Maureen
authors: M
authors: van den Donk
authors: Linette
authors: L
authors: Pellis
authors: Jimmy W
authors: JW
authors: Crott
authors: Manon
authors: M
authors: van Engeland
authors: Pieter
authors: P
authors: Friederich
authors: Fokko M
authors: FM
authors: Nagengast
authors: Jeroen D
authors: JD
authors: van Bergeijk
authors: Sybrand Y
authors: SY
authors: de Boer
authors: Joel B
authors: JB
authors: Mason
authors: Frans J
authors: FJ
authors: Kok
authors: Jaap
authors: J
authors: Keijer
authors: Ellen
authors: E
authors: Kampman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014498:Uracil / Q000378:metabolism*; D014805:Vitamin B 12 / Q000494:pharmacology
chemical_list: D006710:Homocysteine; D014498:Uracil; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D014805:Vitamin B 12