title: Multitarget stool DNA testing for colorectal-cancer screening.
abstract: BACKGROUND
  An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening.
  
  
  METHODS
  We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings.
  
  
  RESULTS
  Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.
  
  
  CONCLUSIONS
  In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).
authors.affiliation: From the Department of Medicine, Indiana University School of Medicine, the Regenstrief Institute, the Simon Cancer Center, and the Center for Innovation at Roudebush Veterans Affairs Medical Center - all in Indianapolis (T.F.I.); the Departments of Medicine and Epidemiology and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill (D.F.R.); the Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York (S.H.I.); Kaiser Permanente Medical Center, Walnut Creek, CA (T.R.L.); Boston Biostatistics Research Foundation, Framingham MA (P.L.); Exact Sciences, Madison, WI (G.P.L., B.M.B.); and the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (D.A.A.).
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Imperiale
authors.forename: David F
authors.initials: DF
authors.lastname: Ransohoff
authors.forename: Steven H
authors.initials: SH
authors.lastname: Itzkowitz
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Levin
authors.forename: Philip
authors.initials: P
authors.lastname: Lavin
authors.forename: Graham P
authors.initials: GP
authors.lastname: Lidgard
authors.forename: David A
authors.initials: DA
authors.lastname: Ahlquist
authors.forename: Barry M
authors.initials: BM
authors.lastname: Berger
mesh_terms: D000199:Actins / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D055398:Bone Morphogenetic Protein 3 / Q000235:genetics; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods*; D005243:Feces / Q000737:chemistry*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007158:Immunologic Techniques; D008297:Male; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009780:Occult Blood; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D000199:Actins; C525757:BMP3 protein, human; D055398:Bone Morphogenetic Protein 3; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D009124:Muscle Proteins; C431705:NDRG4 protein, human; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins