Variables associated with detection of methylated BCAT1 or IKZF1 in blood from patients without colonoscopically-evident colorectal cancer.

Background: DNA methylated in BCAT1 and IKZF1 are promising circulating tumor DNA (ctDNA) biomarkers for colorectal cancer (CRC) detection. This study tested for variables that might be associated with their detection in patients without colonoscopically-evident CRC- so-called "false positives". Methods: A retrospective review of demographic and clinical variables was conducted on patients who were assayed for these biomarkers prior to a colonoscopy for any indication. Potential relationships between detection of these biomarkers and patient variables in patients without CRC were identified by logistic regression. An age-sex-matched case-control study was undertaken to identify additional associations. Results: 196 out of 1593 patients undergoing colonoscopy were positive for BCAT1 and/or IKZF1 methylation; 70 (35.7%) had confirmed diagnosis of CRC. Of the 126 false positives, biomarker levels were significantly lower than in those with CRC (p 70y was the only demographic variable associated with biomarker detection (OR 4.31, 95%CI 1.50-12.41). No significant associations were seen with medications or comorbidities (p>0.05). Four cases without colonoscopically-evident CRC but with biomarker levels above the median for CRC patients were diagnosed with metastatic adenocarcinoma within 1 year. Conclusion: False positive results were most commonly associated with detection of methylated BCAT1 only, as well as age >70y. Impact: In the absence of colonoscopically-evident CRC, a high level of circulating methylated DNA warrants investigations for cancers at other sites.