Circulating free DNA in a screening program for early colorectal cancer detection

Area of Science:

• Oncology
• Molecular Diagnostics
• Gastroenterology

Background:

• Circulating free DNA (cfDNA) analysis offers a noninvasive approach for colorectal cancer (CRC) detection and monitoring.
• The utility of cfDNA in identifying early-stage malignant and premalignant colorectal lesions remains under investigation.

Purpose of the Study:

• To evaluate the predictive value of cfDNA quantification and KRAS mutation status for detecting early colorectal lesions in plasma.
• To assess cfDNA's potential in high-risk individuals screened for CRC.

Main Methods:

• 170 high-risk individuals (>50 years, FOBT-positive) underwent endoscopic examination.
• Plasma cfDNA was quantified using quantitative real-time PCR.
• KRAS mutations in cfDNA were analyzed using mutant-enriched PCR and compared with tissue samples.

Main Results:

• cfDNA levels demonstrated satisfactory predictive capability for adenocarcinomas (AUC 0.709).
• Predictive capability was limited for high-grade intraepithelial neoplasia (HGIN) and premalignant lesions.
• Plasma KRAS mutation detection rate (3%) was significantly lower than in matched tumor tissues (45%).

Conclusions:

• cfDNA quantification shows potential for early adenocarcinoma detection in high-risk, FOBT-positive individuals.
• Enhanced sensitivity is required for cfDNA methods to improve detection of early colorectal lesions, including premalignant ones.