1. ¹Nutritional Sciences Research Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, UK
2. ²Department of Surgery, King's College Hospital, Denmark Hill, London SE5 9RS, UK
3. ³Cancer Research UK Epidemiology Unit, The Radcliffe Infirmary, Oxford OX2 6HE, UK
4. ⁴LGC Limited, Queens' Road, Teddington, Middlesex TW11 0LY, UK

Correspondence: Dr M Pufulete, E-mail: maria.pufulete@kcl.ac.uk

Received 18 November 2004; Revised 10 January 2005; Accepted 11 January 2005; Published online 22 February 2005.

Abstract

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=-0.573, P<0.001 and r=-0.307, P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=-0.311, P=0.01 and r=-0.356, P=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=0.07 and P=0.08, respectively).