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Gut doi:10.1136/gutjnl-2012-304149
  • Colorectal cancer
  • Original article

Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer

  1. for the PRESEPT Clinical Study Steering Committee, Investigators and Study Team
  1. 1Department of Environmental Health Sciences, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA
  2. 2Houston Area Translational Research Consortium, Rice University, Houston, Texas, USA
  3. 3Epigenomics Inc, Seattle, Washington, USA
  4. 4Santaurus Inc, San Diego, California, USA
  5. 5Charité Campus Mitte, Charité Comprehensive Cancer Centre, Berlin, Germany
  6. 6Trial Architecture Consulting, Washington, DC, USA
  7. 7Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
  8. 8Atlanta Gastroenterology Associates, Atlanta, Georgia, USA
  9. 9Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
  10. 10Departments of Epidemiology and Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  1. Correspondence to Professor T R Church, Department of Environmental Health Sciences, University of Minnesota School of Public Health, 1162 Mayo, 420 Delaware St SE, Minneapolis, MN 55455, USA; trc{at}cccs.umn.edu
  • Received 12 November 2012
  • Revised 10 January 2013
  • Accepted 16 January 2013
  • Published Online First 13 February 2013

Abstract

Background As screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in a screening setting.

Objective We prospectively assessed the accuracy of circulating methylated SEPT9 DNA (mSEPT9) for detecting CRC in a screening population.

Design Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma samples before colon preparation. Using a commercially available assay, three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified random sample of other subjects in duplicate real time PCRs. The primary outcomes measures were standardised for overall sensitivity and specificity estimates.

Results 7941 men (45%) and women (55%), mean age 60 years, enrolled. Results from 53 CRC cases and from 1457 subjects without CRC yielded a standardised sensitivity of 48.2% (95% CI 32.4% to 63.6%; crude rate 50.9%); for CRC stages I–IV, values were 35.0%, 63.0%, 46.0% and 77.4%, respectively. Specificity was 91.5% (95% CI 89.7% to 93.1%; crude rate 91.4%). Sensitivity for advanced adenomas was low (11.2%).

Conclusions Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening. However, the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas.

Clinical Trial Registration Number: NCT00855348


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