title: Next-generation stool DNA test accurately detects colorectal cancer and large adenomas.
abstract: OBJECTIVE
  Technical advances have led to stool DNA (sDNA) tests that might accurately detect neoplasms on both sides of the colorectum. We assessed colorectal neoplasm detection by a next-generation sDNA test and effects of covariates on test performance.
  
  
  METHODS
  We performed a blinded, multicenter, case-control study using archived stool samples collected in preservative buffer from 252 patients with colorectal cancer (CRC), 133 with adenomas ≥ 1 cm, and 293 individuals with normal colonoscopy results (controls); two-thirds were randomly assigned to a training set and one-third to a test set. The sDNA test detects 4 methylated genes, a mutant form of KRAS, and the α-actin gene (as a reference value) using quantitative, allele-specific, real-time target and signal amplification; it also quantifies hemoglobin. We used a logistical model to analyze data.
  
  
  RESULTS
  The sDNA test identified 85% of patients with CRC and 54% of patients with adenomas ≥1 cm with 90% specificity. The test had a high rate of detection for all nonmetastatic stages of CRC (aggregate 87% detection rate for CRC stages I-III). Detection rates increased with adenoma size: 54% ≥ 1 cm, 63% >1 cm, 77% >2 cm, 86% >3 cm, and 92% >4 cm (P < .0001). Based on receiver operating characteristic analysis, the rate of CRC detection was slightly greater for the training than the test set (P = .04), whereas the rate of adenoma detection was comparable between sets. Sensitivities for detection of CRC and adenoma did not differ with lesion site.
  
  
  CONCLUSIONS
  Early-stage CRC and large adenomas can be detected throughout the colorectum and with high levels of accuracy by the sDNA test. Neoplasm size, but not anatomical site, affected detection rates. Further studies are needed to validate the findings in a larger population and optimize the sDNA test.
authors: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. ahlquist.david@mayo.edu
authors: David A
authors: DA
authors: Ahlquist
authors: Hongzhi
authors: H
authors: Zou
authors: Michael
authors: M
authors: Domanico
authors: Douglas W
authors: DW
authors: Mahoney
authors: Tracy C
authors: TC
authors: Yab
authors: William R
authors: WR
authors: Taylor
authors: Malinda L
authors: ML
authors: Butz
authors: Stephen N
authors: SN
authors: Thibodeau
authors: Linda
authors: L
authors: Rabeneck
authors: Lawrence F
authors: LF
authors: Paszat
authors: Kenneth W
authors: KW
authors: Kinzler
authors: Bert
authors: B
authors: Vogelstein
authors: Niels Chr
authors: NC
authors: Bjerregaard
authors: Søren
authors: S
authors: Laurberg
authors: Henrik Toft
authors: HT
authors: Sørensen
authors: Barry M
authors: BM
authors: Berger
authors: Graham P
authors: GP
authors: Lidgard
mesh_terms: D000199:Actins / Q000235:genetics; D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D055398:Bone Morphogenetic Protein 3 / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D005243:Feces; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D021141:Nucleic Acid Amplification Techniques; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D014746:Vimentin / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D000199:Actins; C525757:BMP3 protein, human; D014408:Biomarkers, Tumor; D055398:Bone Morphogenetic Protein 3; D005819:Genetic Markers; D006023:Glycoproteins; C117307:KRAS protein, human; D009124:Muscle Proteins; C431705:NDRG4 protein, human; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D014746:Vimentin; C021240:tissue-factor-pathway inhibitor 2; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins