Detection of Hypermethylated DNA or Cyclooxygenase-2 Messenger RNA in Fecal Samples of Patients With Colorectal Cancer or Polyps

• Published in: The American journal of gastroenterology Vol. 102; no. 5; pp. 1070 - 1076
• Main Authors: Leung, Wai K., To, Ka-Fai, Man, Ellen P. S., Chan, Michael W. Y., Hui, Aric J., Ng, Simon S. M., Lau, James Y. W., Sung, Joseph J. Y.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing 01.05.2007; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Aged; Biological and medical sciences; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - enzymology; Cyclooxygenase 2 - analysis; Digestive system. Abdomen; DNA Methylation; DNA, Neoplasm - analysis; Endoscopy; Feces; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Intestinal Polyps - diagnosis; Intestinal Polyps - enzymology; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; Rectal disease; Enzyme; Cyclooxygenase 2; Colorectal cancer; Malignant tumor; Colonic disease; Polymerase chain reaction; Colorectal adenoma; Messenger RNA; Colonoscopy; DNA; Gastroenterology; Digestive diseases; Intestinal disease; Oxidoreductases; Benign neoplasm; Endoscopy; Molecular biology; Reverse transcription polymerase chain reaction; Polyp
• ISSN: 0002-9270; 1572-0241
• DOI: 10.1111/j.1572-0241.2007.01108.x

Detection of fecal DNA is a promising approach to colorectal cancer screening. However, the sensitivity of current fecal DNA tests for colorectal polyps is low. We evaluated the feasibility of detecting aberrantly methylated DNA or cyclooxygenase-2 (COX-2) mRNA in feces of patients with colorectal cancer or polyps. Fecal samples were collected prior to colonoscopy from 20 patients with colorectal cancer, 30 patients with colorectal polyps, and 30 subjects with normal colonic examination. Presence of hypermethylated DNA in 7 tumor-related genes (APC, ATM, hMLH1, sFRP2, HLTF, MGMT, and GSTP1) in stool was analyzed by methylation-specific PCR. COX-2 mRNA in fecal samples was detected by RT-PCR. With the use of this panel of methylation markers, the sensitivity of detecting colorectal cancer and adenoma was 75% (95% CI 50.9-91.3%) and 68% (95% CI 46.5-85.1%), respectively. Three normal subjects also had methylated DNA detected in stool, which gives a specificity of 90% (95% CI 73.5-97.9%). The mean number of genes methylated in DNA from the stool of patients with colorectal cancer and adenoma was 1.4 and 0.9, respectively. In contrast, COX-2 mRNA was detected in the stool samples of 10 (50%) cancer patients and one (4%) patient with advanced adenoma only. Two (6.7%) stool samples from normal subjects also had COX-2 mRNA detected. Detection of aberrantly methylated DNA in fecal samples is more sensitive than COX-2 mRNA for detection of colorectal cancer and adenoma.