No abstract

Background and aims: A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia. The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a randomised, double blind, placebo controlled, parallel design. Methods: Subjects were randomised to receive either 400 mg/day folic acid supplement (n = 15) or placebo (n = 16) for 10 weeks. Genomic DNA methylation, serum and erythrocyte folate, and plasma homocysteine concentrations were measured at baseline and post intervention. Results: Folic acid supplementation increased serum and erythrocyte folate concentrations by 81% (95% confidence interval (CI) 57-104%; p,0.001 v placebo) and 57% (95% CI 40-74%; p,0.001 v placebo), respectively, and decreased plasma homocysteine concentration by 12% (95% CI 4-20%; p = 0.01 v placebo). Folic acid supplementation resulted in increases in DNA methylation of 31% (95% CI 16-47%; p = 0.05 v placebo) in leucocytes and 25% (95% CI 11-39%; p = 0.09 v placebo) in colonic mucosa. Conclusions: These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid.

DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C-T and 1298A-C), methionine synthase (MS 2756A-G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36 -78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r ¼ À0.573, Po0.001 and r ¼ À0.307, P ¼ 0.01 respectively) and DNA hypomethylation in colonic mucosa (r ¼ À0.311, P ¼ 0.01 and r ¼ À0.356, P ¼ 0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P ¼ 0.07 and P ¼ 0.08, respectively).

Serum vitamin B-12 but not folate status may be associated with ERalpha promoter methylation in normal-appearing colorectal mucosa.

Biliary reconstruction affords satisfactory long-term outcome. The likelihood of needing the access loop for radiological intervention is dependent on the Bismuth level. The authors recommend that an access loop be constructed in all patients with Bismuth level III and IV injuries.