Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial

Abstract

OBJECTIVES: Dietary folate intake is inversely associated with the risk of colorectal cancer. This study investigated the effect of folate supplementation on genomic DNA methylation and DNA strand breaks in exons 5–8 of the p53 gene of the colonic mucosa, two provisional biomarkers of colon cancer. METHODS: Twenty subjects with adenomas were randomized to receive either folate (5 mg/day) or placebo for 1 yr after polypectomy. At baseline, 6 months and 1 yr, systemic and colonic measures of folate status were determined, as were the biomarkers mentioned earlier. RESULTS: Folate supplementation increased serum, red blood cell and colonic mucosal folate concentrations ( p < 0.02). Folate supplementation also increased the extent of genomic DNA methylation at 6 months and 1 yr ( p = 0.001), whereas placebo administration was associated with an increase in the extent of genomic DNA methylation only at 1 yr. Similarly, folate supplementation decreased the extent of p53 strand breaks in exons 5–8 at 6 months and 1 yr ( p < 0.02), whereas placebo administration was associated with a decrease in the extent of p53 strand breaks only at 1 yr. CONCLUSIONS: Both of these provisional biomarkers of colon cancer underwent accelerated improvement at 6 months with folate supplementation. However, these markers also improved with placebo at 1 yr. Therefore, potential confounding factors that seem to modulate these biomarkers need to be identified and corrected in order for these markers to serve as suitable surrogate endpoints in folate chemoprevention trials.