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Detection of Epigenetic Changes in Fecal DNA as a Molecular Screening Test for Colorectal Cancer: A Feasibility Study

Departments of¹ Medicine & Therapeutics,² Anatomical and Cellular Pathology, and³ Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong;

^aaddress correspondence to this author at: Department of Medicine & Therapeutics, Prince of Wales Hospital, 30-32 Ngan Shing St., Shatin, Hong Kong; fax 852-2637-3852, e-mail wkleung@cuhk.edu.hk

The first 300 words of the full text of this article appear below.

Colorectal cancer is the fourth most common cancer worldwide (1). There has been intense interest in the search for potential tumor markers that can be used in the screening of colorectal cancer. Because of the continuous shedding of intestinal cells into the lumen, genetic alterations found in tumors can also been detected in stool, which offers a golden opportunity for the noninvasive screening of colorectal cancer. Previous studies have demonstrated the feasibility of detecting altered DNA, including BAT26, APC, K-ras, and p53 mutations, in the feces of colorectal cancer patients (2)(3)(4)(5).

Epigenetic gene silencing by promoter hypermethylation is increasingly recognized to play a crucial role in carcinogenesis (6). In colorectal cancer, several tumor-related genes have been found to have promoter hypermethylation in the CpG islands (7)(8)(9)(10). These epigenetic changes are detected in the early phase of colorectal cancer development before the development of K-ras mutations (11). We tested the feasibility of detecting promoter hypermethylation of multiple tumor-related genes in fecal DNA of patients with colorectal cancer.

We recruited 20 colorectal cancer patients (mean age, 69 years; range, 45–90 years; 7 males). Patients who had familial adenomatous polyposis or hereditary nonpolyposis colon cancer, inflammatory bowel diseases, or previous colon surgery were excluded. Colon tumor biopsies were obtained during colonoscopy. Stool samples were collected before initiation of bowel preparation. The stool specimens were stored in a household freezer and then transferred for long-term storage at –80 °C. Twenty age-matched controls were randomly selected from individuals who participated in a colonoscopy screening program during the same period and had normal colonoscopy results (12). Stool samples were collected before bowel preparation as described for cancer . . . [Full Text of this Article]

The following articles in journals at HighWire Press have cited this article:

				H. Zou, J. J. Harrington, A. M. Shire, R. L. Rego, L. Wang, M. E. Campbell, A. L. Oberg, and D. A. Ahlquist Highly Methylated Genes in Colorectal Neoplasia: Implications for Screening Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2686 - 2696. [Abstract] [Full Text] [PDF]

				H. Zou, J. Harrington, R. L. Rego, and D. A. Ahlquist A Novel Method to Capture Methylated Human DNA from Stool: Implications for Colorectal Cancer Screening Clin. Chem., September 1, 2007; 53(9): 1646 - 1651. [Abstract] [Full Text] [PDF]