Yi. Kim et al., Effects of folate supplementation on two provisional molecular markers of colon cancer: A prospective, randomized trial, AM J GASTRO, 96(1), 2001, pp. 184-195
OBJECTIVES: Dietary folate intake is inversely associated with the risk of
colorectal cancer. This study investigated the effect of folate supplementa
tion on genomic DNA methylation and DNA strand breaks in exons 5-8 of the p
53 gene of the colonic mucosa, two provisional biomarkers of colon cancer.
METHODS: Twenty subjects with adenomas were randomized to receive either fo
late (5 mg/day) or placebo for 1 yr after polypectomy. At baseline, 6 month
s 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 incr
eased 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 ex
tent of genomic DNA methylation only at 1 yr. Similarly, folate supplementa
tion 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 decr
ease 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 conf
ounding factors that seem to modulate these biomarkers need to be identifie
d and corrected in order for these markers to serve as suitable surrogate e
ndpoints in folate chemoprevention trials. (Am J Gastroenterol 2001;96:184-
195. (C) 2001 by Am. Coll. of Gastroenterology).