NEW ORLEANS -- Research teams led by Mayo Clinic have demonstrated for the first time that two types of colorectal pre-cancers 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 an important type of colorectal pre-cancer called serrated polyps. The findings were presented at Digestive Disease Week 2010 (http://www.ddw.org/wmspage.cfm?parm1=679), the annual meeting of the American Gastroenterological Association.
VIDEO ALERT: Additional audio and video resources, including excerpts from an interview with Dr. David Ahlquist describing the research, are available on the Mayo Clinic News Blog (http://newsblog.mayoclinic.org/?p=3208&preview=true ). These materials also are subject to embargo, but may be accessed in advance by journalists for incorporation into stories. The password for this post is Ahlquist4.
David Ahlquist, M.D. (http://www.mayoclinic.org/bio/10006044.html), a gastroenterologist with Mayo Clinic and the senior investigator, said that sensitive stool DNA test methods developed at Mayo Clinic can detect common forerunners of colorectal cancer. "Detection of precursor lesions during screening is essential if cancer prevention is the goal," Dr. Ahlquist says.
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).
Detection of Colorectal Precancerous Lesions in Inflammatory Bowel Disease (Embargoed until DDW presentation, May 3, 2010, 5:30 p.m. CT)
The first study, presented on May 3 at Digestive Disease Week, involves identifying both cancer and a precancerous lesion, called dysplasia, in people who suffer from IBD. In a blinded study with 10 cases and 10 controls done in conjunction with Mount Sinai Medical Center and the University of Chicago, 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 pre-cancer in IBD can be detected noninvasively," says Dr. Ahlquist. "The 90 percent 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."
Detection of Serrated Colorectal Polyps (Embargoed until DDW presentation, May 4, 3 p.m. CT)
The second study, presented on May 4, 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 says serrated polyps have been ignored or excluded from most screening studies to date because it wasn't clear they were associated with cancer. "Now they are regarded as the forerunner in roughly 30 percent of colon cancers," says 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 results to fecal blood tests on the same specimens.
"We observed a 71 percent detection rate with stool DNA testing," says Dr. Ahlquist. "This was significantly higher than the 7 percent 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 ," says Dr. Ahlquist. "However, findings from both pilot studies need to be corroborated in larger studies."
Collaboration
The studies were funded by the National Institutes of Health and the Charles Oswald Foundation. Mayo Clinic co-authors for the colorectal neoplasia and inflammatory bowel disease study include John Kisiel, M.D.; Tracy Yab; Fareeda Hussain, William Taylor; Jonathan Harrington; Mary Devens; Julie Simonson; Megan Garrity-Park; William Sandborn, M.D. (http://www.mayoclinic.org/bio/10948686.html); Edward Loftus, M.D.( http://www.mayoclinic.org/bio/10640339.html); and Hongzhi Zou, M.D., PhD. Co-authors for the serrated colorectal polyps study include Hussain, Yab, Harrington, Taylor, Thomas Smyrk, M.D. (http://www.mayoclinic.org/bio/10030808.html); Douglas Mahoney; and Dr. Zou.
Disclosure
Drs. D. Ahlquist and D. Zou, Mses. T. Yab and F. Hussain; and Messrs. Taylor and Harrington and Mayo Clinic have a financial interest related to technology used with this research. This technology has been licensed to Exact Sciences. Mayo Clinic stands to receive royalties from the licensing of this technology and holds an equity position in Exact Sciences.
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