Original Contribution
The American Journal of Gastroenterology (2007) 102, 1070–1076; doi:10.1111/j.1572-0241.2007.01108.x
Detection of Hypermethylated DNA or Cyclooxygenase-2 Messenger RNA in Fecal Samples of Patients With Colorectal Cancer or Polyps
Wai K Leung MD, FACG, Ka-Fai To MBChB, FRCPA, Ellen P S Man MSc, Michael W Y Chan PhD, Aric J Hui MBChB, MRCP, Simon S M Ng MBChB, FRCS, James Y W Lau MD, FRCS and Joseph J Y Sung MD, PhD, FACG
Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
Correspondence: Wai K Leung, MD, FACG, Department of Medicine & Therapeutics, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong.
Received 18 September 2006; Accepted 21 November 2006.
Abstract
BACKGROUND:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSION:
Detection of aberrantly methylated DNA in fecal samples is more sensitive than COX-2 mRNA for detection of colorectal cancer and adenoma.
