Stool DNA Testing Could Play Expanded Role in Colon Cancer Prevention

Research teams have demonstrated for the first time that two types of colorectal precancers can be detected through noninvasive stool DNA testing. The two studies being presented demonstrate that stool DNA testing may be useful for detection of premalignant dysplasia in patients with inflammatory bowel disease (IBD) and of a significant type of colorectal precancer called serrated polyps.

David Ahlquist, M.D., a gastroenterologist with Mayo Clinic (Rochester, MN, USA) and the senior investigator, reported that sensitive stool DNA test techniques developed at Mayo Clinic could detect common forerunners of colorectal cancer. “Detection of precursor lesions during screening is essential if cancer prevention is the goal,” Dr. Ahlquist stated.

Compared to widely used fecal blood tests, stool DNA testing has higher detection rates for curable stage colorectal cancer and for common precancerous polyps (called adenomas).

The first study, presented on May 3, 2010, at Digestive Disease Week, the annual meeting of the American Gastroenterological Association held in New Orleans, LA, USA, involved identifying both cancer and a precancerous lesion, called dysplasia, in individuals who suffer from IBD. In a blinded study with 10 cases and 10 controls conducted in conjunction with Mount Sinai Medical Center (New York, NY, USA) and the University of Chicago (IL, USA), researchers found that stool DNA testing was positive in nine out of 10 cases (five of five with cancer, and four of five with dysplasia).

“This study shows that cancer and precancer in IBD can be detected noninvasively,” said Dr. Ahlquist. “The 90% detection rate by stool DNA testing is remarkable. It’s important for people with IBD because they are at much higher risk for colorectal cancer than the general population. Given the limitations of colonoscopies in detecting these lesions, stool DNA testing could play a complementary role to improve the effectiveness of cancer surveillance.”

The second study, presented on May 4, 2010, involves detecting serrated colorectal polyps. Unlike common adenomas, which usually protrude from the colon lining and are easy to see, serrated polyps are typically flat and the same color as the colon lining. Dr. Ahlquist remarked that serrated polyps have been ignored or excluded from most screening studies to date because it was not clear they were associated with cancer. “Now they are regarded as the forerunner in roughly 30% of colon cancers,” said Dr. Ahlquist. “Most of these are located on the right side of the colon, where screening has had less impact historically.”

For this study, researchers first took tissue and identified two genetic markers that were present in serrated polyps but not in normal colon. The team assayed the markers (mutant BRAF and methylated vimentin genes) in stool samples from 14 cases and 19 control patients who had undergone screening colonoscopies. In blinded fashion, they compared the findings to fecal blood tests on the same specimens.

“We observed a 71% detection rate with stool DNA testing,” noted Dr. Ahlquist. “This was significantly higher than the 7% rate with conventional fecal blood tests. Detection of these important types of precancer by stool DNA testing offers promise in our efforts to more effectively and affordably prevent colorectal cancer. However, findings from both pilot studies need to be corroborated in larger studies.”