Browsing by Subject "Ulcerative Colitis"

Background- Colorectal cancer (CRC) is the third most common epithelial carcinoma. There is an increased risk of colorectal cancer in people with longstanding inflammation in the large intestine, including individuals with ulcerative colitis (UC). Epigenetic changes in CRC such as aberrant DNA methylation alterations are common changes in human cancer. The aim of this study is to identify the DNA methylation alterations of selected inflammation related genes in UC-CRC vs. Lynch syndrome (LS). Method- DNA was extracted from archival tissue specimens from normal and tumor samples from UC-CRC (n= 31), and LS-CRC (n=29). Methylation-specific multiple ligation-dependent probe amplification (MS-MLPA) assays were used to detect CIMP status and CpG promoter methylation status of seven inflammation related genes. Microsatellite instability analysis was carried out using two mononucleotide repeat markers BAT25 and BAT26. Results- Increased hypermethylation frequencies in carcinoma vs. normal colonic mucosa were detected for all the inflammatory marker genes in specimens of UC-CRC patients. Statistically significant differences for methylation frequencies were observed in the NTSR1 gene (p value =0.008) and SOCS2 gene (p value =0.04) in specimens of UC-CRC patients. NTSR1 gene showed significantly increased methylation of normal colonic mucosae from UC-CRC vs. LS patients (p value=0.01). Conclusion- UC-CRC and LS tumor specimens revealed varying frequencies of hypermethylation in all the inflammatory genes. Methylation of the NTSR1 in the normal colonic mucosa suggests a possible field defect in UC-CRC, and could thus be used as an early biomarker to detect increased UC-CRC risk in non-neoplastic epithelium.