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Applied Research and Development

Studies of Stool-Based DNA Screening 
 
The Science Behind Stool-Based DNA Screening 
 
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The Science Behind Stool-Based DNA Screening

Over the past decade, intense research has shown the underlying basis of colorectal cancer to be an accumulation of genetic alterations. Approximately 75%–85% of colorectal cancers are sporadic (not inherited), but cancer is a disease of the genome, i.e. every cancerous cell has some genetic alteration. This knowledge of genomics forms the basis of this new method of CRC screening. Known DNA alterations associated with colorectal neoplasia can be identified.

The graphic below describes groundbreaking work by Dr. Bert Vogelstein— the leader in the field of cancer genetics.

click here to enlarge chart

This “Vogelgram,” as it is called, details the specific molecular events of carcinogenesis—the transition of a normal cell in the epithelial lining of the colon through early and late adenoma and early and late cancer. The dwell stage of colorectal cancer in the average-risk person is thought to be approximately 8-10 years. This provides a large window of opportunity for screening, which can lead to early detection and even prevention of the disease.

Specific DNA alterations (APC, K-ras, p53 and BAT-26) occur as discrete steps in this cascade. By identifying these stages, Dr Vogelstein’s work has allowed the development of an analytical technique based largely on these genetic markers of colorectal neoplasia.

Rapidly growing cells in cancers and adenomas, which contain altered DNA, are continuously shed into the large bowel lumen and passed in the feces. DNA is stable in stool and, remarkably, this colorectal cancer-associated DNA can be isolated from the bacterial DNA in stool.

The Stool-Based DNA Screening Approach

Here’s how it works:
Every day millions of normal epithelial cells are shed from the colon wall into the stool stream and, as they degenerate, release their DNA.

As polyps develop, they also shed cells into the stool stream. Some of these cells contain altered DNA reflecting acquired mutations associated with colorectal neoplasia. Imagine a potentially cancerous polyp developing in the transverse colon beyond the reach of the flexible sigmoidoscope. Unlike bleeding, which may occur from time to time if at all, the cells from this potentially cancerous polyp are shed continuously, and can provide a detectable amount of altered DNA in the stool specimen.

A stool-based DNA screening test is prescribed by a healthcare provider and the patient collects a single whole stool in the materials provided. The specimen is then forwarded to a laboratory for analysis.

Through a series of sophisticated laboratory procedures, the specimen is homogenized and purified, and specific DNA targets are isolated. Target DNA is then amplified and analyzed for molecular alterations associated with cancer and pre-cancerous conditions of the colon and rectum. If a DNA abnormality is identified, colonoscopy must be performed.

Although the science behind stool-based DNA screening is very sophisticated, the specimen collection process is very simple. Sample collection requires:

• Single whole stool specimen
• No bowel preparation
• No medication or dietary restrictions
• No sample manipulation

By simplifying the routine screening process, stool-based DNA screening directly addresses patient non-compliance issues. As a result, more patients may be safely screened without the discomfort and inconvenience often associated with invasive procedures. Greater compliance, in turn, may lead to earlier detection of colorectal cancer and a reduction in mortality rates associated with colorectal cancer.

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