PMID- 30336540
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20190909
IS  - 1433-6510 (Print)
IS  - 1433-6510 (Linking)
VI  - 64
IP  - 10
DP  - 2018 Oct 1
TI  - Early Detection of Colorectal Cancer: a Multi-Center Pre-Clinical Case Cohort 
      Study for Validation of a Combined DNA Stool Test.
PG  - 1719-1730
LID - 10.7754/Clin.Lab.2018.180521 [doi]
AB  - BACKGROUND: Although colonoscopy-based screening has proven to be highly 
      effective in detecting colorectal cancer (CRC), participation rates remain 
      disappointing. Development of CRC is associated with a number of genetic or 
      somatic mutations. New, non-invasive stool tests are currently being developed 
      based on the detection of these alterations. We investigated if a non-invasive 
      stool assay can offer sufficient sensitivity and specificity to supplement 
      colonoscopy-based screening. METHODS: We compared a combined stool assay, which 
      incorporates fecal occult blood testing (FOBT), quantification of human DNA 
      (hDNA) as well as detection of genetic mutations of KRAS and BRAF (Combined DNA 
      stool assay), with commercially available FOBT and M2-PK tests in a multi-centric 
      six-armed pre-clinical case cohort study. Seven hundred thirty-four patients were 
      recruited prior to elective/screening colonoscopy or prior to surgery in case of 
      a recent CRC diagnosis. According to clinical assessment and 
      colonoscopy/histology results, the following groups were assigned: controls, 
      irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hyperplastic 
      polyps, adenomas, and CRC. Finally, 566 out of 734 patients (77.1%) were screened 
      for CRC and overall gut status via colonoscopy, FOBT, M2-PK, with combined 
      FOBT/M2-PK and the Combined DNA stool assay as described here. RESULTS: All 
      sensitivities and specificities are measured against histologically confirmed 
      results by colonoscopy. Confirmed sensitivities for detecting colorectal cancer 
      were 68% with FOBT, 83% with M2-PK, 90% with combined FOBT and M2-PK, and 85% 
      with the Combined DNA stool assay. Specificities were 96% with FOBT, 61% with 
      M2-PK, 62% with combined FOBT and M2-PK, and 92% with the Combined DNA stool 
      assay in the control group with no pathological findings during colonoscopy. 
      CONCLUSIONS: The Combined DNA stool assay detects CRC with a significantly higher 
      Youden Index than the other reviewed non-invasive screening options. The results 
      also suggest that the Combined DNA stool assay represents a reliable assay for 
      detecting colorectal cancer, sufficient to be recommended as a supplement to 
      colonoscopy screening.
FAU - Dollinger, Matthias M
AU  - Dollinger MM
FAU - Behl, Susanna
AU  - Behl S
FAU - Fleig, Wolfgang E
AU  - Fleig WE
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PL  - Germany
TA  - Clin Lab
JT  - Clinical laboratory
JID - 9705611
RN  - 0 (DNA, Neoplasm)
RN  - 0 (KRAS protein, human)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cohort Studies
MH  - Colonoscopy/*methods
MH  - Colorectal Neoplasms/*diagnosis/genetics
MH  - DNA, Neoplasm/*analysis
MH  - Early Detection of Cancer/*methods
MH  - Feces/*chemistry
MH  - Female
MH  - Humans
MH  - Male
MH  - Mass Screening/methods
MH  - Middle Aged
MH  - Mutation
MH  - *Occult Blood
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Proto-Oncogene Proteins p21(ras)/genetics
MH  - Sensitivity and Specificity
EDAT- 2018/10/20 06:00
MHDA- 2019/09/10 06:00
CRDT- 2018/10/19 06:00
PHST- 2018/10/19 06:00 [entrez]
PHST- 2018/10/20 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
AID - 10.7754/Clin.Lab.2018.180521 [doi]
PST - ppublish
SO  - Clin Lab. 2018 Oct 1;64(10):1719-1730. doi: 10.7754/Clin.Lab.2018.180521.