Folic acid mediated attenuation of loss of heterozygosity of DCC tumor suppressor gene in the colonic mucosa of patients with colorectal adenomas

Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial

“…We have observed that folate supplementation prevented the loss of heterozygosis (LOH) of the DCC gene in 5 out of 5 patients who demonstrated baseline heterozygosis, whereas 2 out of 4 placebo treated patients with baseline heterozygosis demonstrated complete allelic loss. Mucosal protein levels of DCC were also reduced in 70% of placebo treated patients compared to only 10% of folate treated patients [34] . Cell culture studies have further demonstrated that supplemental folic acid and its metabolite 5-methyltetrahydrofolate (5-MTF) inhibit EGF-receptor (EGFR) promoter activity in colon cancer HCT-116 cells by enhancing methylation [35] .…”

“…The restoration of DNA methylation status in patients with colorectal neoplasms treated with supraphysiological doses of folic acid lends further support to the hypothesis. In a recent study, we examined the changes in mutational status of APC, DCC and p53 genes in macroscopically normal appearing rectal mucosa at baseline and after 1 year of treatment with either folic acid or placebo [34] . We have observed that folate supplementation prevented the loss of heterozygosis (LOH) of the DCC gene in 5 out of 5 patients who demonstrated baseline heterozygosis, whereas 2 out of 4 placebo treated patients with baseline heterozygosis demonstrated complete allelic loss.…”

Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate's Role

“…Folic acid intake has been reported to prevent loss of heterozygosity of a tumor suppressor gene in a small supplementation trial in humans (115). Folate depletion of human tissue culture cells can result not only in the expected global hypomethylation (116,117) but also targeted hypermethylation of the H-cadherin locus (117).…”

Loss of heterozygosity of Kras2 gene on 12p12-13 in Chinese colon carcinoma patients

“…LOH was detected in 30% (3/10) of adjacent tissue specimens (3,7,10) at least on one marker, 28.5% (2/7) of adjacent tissue specimens on D12S1034, 25% (1/4) on D12S1617, 14.29% (1/7) on D12S1596, 12.5% (1/8) on D12S89, and 0% on other markers (Table 2 and Table 3, Figure 1). …”

“…However, it has been reported that wild type Kras2 gene has inhibitory effects on tumor growth and proliferation [5] . Inactivation of cancer suppressor gene is a frequently encountered early event in the development of tumors, leading to loss of heterozygosity (LOH) [6][7][8][9][10] . This study was to investigate the possible genetic variation of wild type Kras2 gene in the carcinogenesis of colon carcinoma by analyzing LOH in tumor and its adjacent tissues.…”