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Previous Volume 351:2704-2714 December 23, 2004 Number 26 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Woolf, S. H. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Although fecal occult-blood testing is the only available noninvasive screening method that reduces the risk of death from colorectal cancer, it has limited sensitivity. We compared an approach that identifies abnormal DNA in stool samples with the Hemoccult II fecal occult-blood test in average-risk, asymptomatic persons 50 years of age or older.

Methods Eligible subjects submitted one stool specimen for DNA analysis, underwent standard Hemoccult II testing, and then underwent colonoscopy. Of 5486 subjects enrolled, 4404 completed all aspects of the study. A subgroup of 2507 subjects was analyzed, including all those with a diagnosis of invasive adenocarcinoma or advanced adenoma plus randomly chosen subjects with no polyps or minor polyps. The fecal DNA panel consisted of 21 mutations.

Results The fecal DNA panel detected 16 of 31 invasive cancers, whereas Hemoccult II identified 4 of 31 (51.6 percent vs. 12.9 percent, P=0.003). The DNA panel detected 29 of 71 invasive cancers plus adenomas with high-grade dysplasia, whereas Hemoccult II identified 10 of 71 (40.8 percent vs. 14.1 percent, P<0.001). Among 418 subjects with advanced neoplasia (defined as a tubular adenoma at least 1 cm in diameter, a polyp with a villous histologic appearance, a polyp with high-grade dysplasia, or cancer), the DNA panel was positive in 76 (18.2 percent), whereas Hemoccult II was positive in 45 (10.8 percent). Specificity in subjects with negative findings on colonoscopy was 94.4 percent for the fecal DNA panel and 95.2 percent for Hemoccult II.

Conclusions Although the majority of neoplastic lesions identified by colonoscopy were not detected by either noninvasive test, the multitarget analysis of fecal DNA detected a greater proportion of important colorectal neoplasia than did Hemoccult II without compromising specificity.

Source Information

From the Department of Medicine, Indiana University, and the Regenstrief Institute — both in Indianapolis, (T.F.I.); the Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill (D.F.R.); the Department of Medicine, Mount Sinai School of Medicine, New York (S.H.I.); CareStat, Newton, Mass. (B.A.T.); and Exact Sciences, Marlborough, Mass. (M.E.R.).

Address reprint requests to Dr. Imperiale at the Regenstrief Institute, 1050 Wishard Blvd., Indianapolis, IN 46202.

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Fecal DNA for Colorectal-Cancer Screening
Frossard J.-L., de Peyer R., Worthley D. L., Cole S. R., Young G. P., Imperiale T. F., Ransohoff D. F., Itzkowitz S. H.
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N Engl J Med 2005; 352:1384-1385, Mar 31, 2005. Correspondence

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