Microsatellite instability in non-neoplastic mucosa of patients with ulcerative colitis: effect of folate supplementation.

Microsatellite instability (MSI) detected in non-neoplastic mucosa of patients with ulcerative colitis has been ascribed to an excess of DNA damage associated with chronic inflammation. Folate deficiency, commonly found in patients with long-standing disease, could further contribute to this defect because folate is essential for DNA replication and repair. We evaluated MSI in the colonic mucosa of 26 patients with ulcerative colitis for >10 yr and 10 patients with Crohn's colitis and correlated MSI with folate status. DNA was amplified using primers directed at nine different loci. Folate concentrations in serum, whole blood, and colonic mucosa were determined using the Lactobacillus casei assay. MSI was found in 3/23 patients (13%) with ulcerative colitis and in none of the patients with Crohn's colitis. All three patients with MSI had inactive histological disease, whereas all patients with active disease were negative for MSI (p = 0.08). Serum, whole blood, and colonic concentrations of folate were 30-50% lower in patients with MSI (p > 0.05), and folate supplements had been administered less frequently during the past 5-yr (p = 0.06). One of the patients with MSI was randomized to receive folate 5 mg/d for 6 months, and a clear change in MSI pattern was observed in three of six markers. A defect in DNA repair associated with a low folate status may be one additional cause for patients with ulcerative colitis exhibiting MSI in non-neoplastic mucosa.