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DNA-based colon cancer screening

IHN logo A screening method for colon cancer using a fecal DNA panel has been found to be more accurate than the standard fecal occult-blood test. Colorectal cancer (cancer of the colon or rectum) is the second leading cause of death from cancer in the US. If caught early (in the polyp stage) it is treatable by surgery. Checking the stool for blood (fecal occult-blood testing) is currently the most widely used screening test for colorectal cancer. However, the test tends to miss a significant portion of cancers since many tumors do not actually bleed. DNA testing has a high degree of accuracy (sensitivity) in patients with symptomatic cancer, but it is not known whether DNA testing would be equally useful in patients with less advanced, non-symptomatic lesions. A team from the Colorectal Cancer Study Group has now compared the results of the standard Hemoccult II (Beckman Coulter) fecal occult-blood test with that of the DNA testing in 4404 asymptomatic patients over 50 years old and at average risk for colorectal cancer. Results were compared to those obtained by colonoscopy, the "gold standard", in a random subgroup of 2507 patients.

Analysis showed that compared to the Hemoccult II test, the accuracy of the fecal DNA panel was four times greater for invasive cancer and more than two times greater for adenomas containing high-grade abnormalities (dysplasia). Of 31 invasive cancers, the fecal DNA panel detected 16 and the Hemoccult II detected 4 (51.6% vs. 12.9%); of 71 invasive cancers plus non-cancerous tumors (adenomas) with high-grade dysplasia, the fecal DNA panel detected 29 and the Hemoccult II detected 10 (40.8% vs. 14.1%); and, of 418 cases of uncontrolled cell growth (advanced neoplasia), the fecal DNA panel detected 76 compared to 45 detected by the Hemoccult II (18.2% vs. 10.8%). Furthermore, the level of accuracy with the fecal DNA panel was achieved with only a minor decrease in correct identification of subjects without disease who had no polyps on colonoscopy. The results suggest that the fecal DNA panel may be more accurate than the Hemoccult II test for the detection of early colorectal cancer, and the researchers note that the availability of a more accurate, non-invasive test might encourage more widespread screening.

Dr. Steven Woolf of Virginia Commonwealth University, in an accompanying editorial, points out that fecal DNA testing is vastly more expensive than fecal occult-blood testing ($400-800 per test compared to $3- 40 per test). He also estimates that colorectal cancer will ultimately only be diagnosed in about 2% of people (aged 50-59 years old) who have a positive fecal DNA test. NOTE: The research was supported by grants from Exact Sciences, the clinical laboratory used to determine results of the fecal DNA panel test for the study.
Imperiale TF, et al. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med. 2004 Dec 23;351(26):2704-14
Woolf SH. A smarter strategy? Reflections on fecal DNA screening for colorectal cancer. N Engl J Med. 2004 Dec 23;351(26):2755-8

Editor's comment: It is somewhat disconcerting, to say the least, that the standard fecal occult-blood test in use today detected less than 13% of invasive colorectal cancers. Clearly, for anyone concerned about colorectal cancer, colonoscopy is a must.

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