Improved Fecal DNA Test for Colorectal Cancer Screening

Steven H. Itzkowitz, Lina Jandorf, Randall Brand, Linda Rabeneck, Paul C. Schroy, Stephen Sontag, David Johnson, Joel Skoletsky, Kris Durkee, Sanford Markowitz, Anthony Shuber

Research output: Contribution to journalArticlepeer-review

202 Scopus citations

Abstract

Background & Aims: Fecal DNA testing has shown greater sensitivity than guaiac-based occult blood tests for noninvasive colorectal cancer (CRC) screening. The prototype assay (version 1), which analyzed 22 gene mutations and DNA integrity assay (DIA), showed a sensitivity of 52% for CRC detection and a specificity of 94% in average-risk individuals. The present study was conducted to determine the sensitivity and specificity of a second-generation assay (version 2) that uses improved DNA stabilization/isolation techniques and a new promoter methylation marker. Methods: Forty patients with CRC and 122 subjects with normal colonoscopy provided stool samples to which DNA preservation buffer was added immediately. DNA was purified using gel-based capture, and analyzed for the original panel of 22 mutations, DIA, and 2 new promoter methylation markers. Results: By using DNA that was optimally preserved and purified from stool, the sensitivity of the prototype version 1 assay increased to 72.5% because of enhanced performance of DIA. Vimentin gene methylation alone provided sensitivity and specificity of 72.5% and 86.9%, respectively. The optimal combination of vimentin methylation plus DIA resulted in 87.5% sensitivity and 82% specificity; cancers were detected regardless of stage or location. False-positive vimentin methylation was associated with older age. Conclusions: An improved fecal DNA test that incorporates only 2 markers shows much higher sensitivity for CRC. The new assay is easier to perform and should be less costly, thereby facilitating its use for noninvasive CRC screening.

Original languageEnglish
Pages (from-to)111-117
Number of pages7
JournalClinical Gastroenterology and Hepatology
Volume5
Issue number1
DOIs
StatePublished - Jan 2007

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