A blood test for methylated BCAT1 and IKZF1 vs. a fecal immunochemical test for detection of colorectal neoplasia

Erin L. Symonds, Susanne K. Pedersen, Rohan T. Baker, David H. Murray, Snigdha Gaur, Stephen R. Cole, Geetha Gopalsamy, Dileep Mangira, Lawrence C. LaPointe, Graeme P. Young

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OBJECTIVES: To compare the performance of a new blood test for colorectal cancer (CRC) to an established fecal immunochemical test (FIT) in a study population with the full range of neoplastic and non-neoplastic pathologies encountered in the colon and rectum. METHODS: Volunteers were asked to complete a FIT prior to colonoscopy. Blood was collected after bowel preparation but prior to colonoscopy, and plasma was assayed for the presence of methylated BCAT1 and IKZF1 DNA using a multiplex real-Time PCR assay. Sensitivity and specificity estimates for the blood test were calculated from true-and false-positive rates for neoplasia and compared with FIT at a range of fecal hemoglobin (Hb) concentration positivity thresholds. RESULTS: In total, 1,381 volunteers (median age 64 years; 49% male) completed both tests prior to colonoscopy. Estimated sensitivity of the BCAT1/IKZF1 blood test for CRC was 62% (41/66; 95% confidence interval 49 74%) with a specificity of 92% (1207/1315; 90 93%). FIT returned the same specificity at a cutoff of 60 μg Hb/g, at which its corresponding sensitivity for cancer was 64% (42/66; 51 75%). In the range of commonly used FIT cutoffs, respective cancer sensitivity and specificity estimates with FIT were: 59% (46 71%) and 93% (92 95%) at 80 μg Hb/g, and 79% (67 88%) and 81% (78 83%) at 10 μg Hb/g. Although estimated sensitivities were not significantly different between the two tests for any stage of cancer, FIT showed a significantly higher sensitivity for advanced adenoma at the lower cutoffs. Specificity of FIT, but not of the BCAT1/IKZF1 blood test, deteriorated substantially in people with overt blood in the feces. When combining FIT (cutoff 10 μg Hb/g) with the BCAT1/IKZF1 blood test, sensitivity for cancer was 89% (79 96%) at 74% (72 77%) specificity. CONCLUSIONS: A test based on detection ofmethylated BCAT1/IKZF1 DNA in blood has comparable sensitivity but better specificity for CRC than FITat the commonly used positivity threshold of 10 μg Hb/g. Further evaluation of the new test relative to FIT in the population screening context is now required to fully understand the potential advantages and disadvantages of these biomarkers in screening.

Original languageEnglish
Article numbere137
Number of pages9
Journalclinical and translational gastroenterology
Issue number1
Publication statusPublished - 1 Jan 2016


  • methylatedBCAT1/IKZF1DNA
  • Colorectal Neoplasia
  • Diagnosis


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