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

Aims and background. The quantification and molecular characterization of circu lating free DNA (cfDNA) have attracted much interest as new and promising, nonin vasive means of detecting and monitoring the presence of surgical resectable col orectal cancer (CRC). Instead, the role of cfDNA in the early detection of malignant and premalignant colorectal lesions is still unclear. The aim of this study was to eval uate the predictive power of the quantification and KRAS status of cfDNA in detecting early colorectal lesions in plasma from healthy high-risk subjects. Methods . The study population consisted of 170 consecutive healthy high-risk sub jects aged >50 years who participated in the screening program promoted by the Lo cal Health Service (ASL-Milano) for early CRC detection and who underwent endo scopic examination after being found positive at fecal occult blood test (FOBT). Thir ty-four participants had malignant lesions consisting of 12 adenocarcinomas (at an early stage in half of the cases) and 22 instances of high-grade intraepithelial neopla sia (HGIN) in adenomas; 73 participants had premalignant lesions (adenomas and hyperplasia), and 63 participants had no lesions. Plasma cfDNA was quantified by quantitative real-time PCR and analyzed for KRAS mutations by a mutant-enriched PCR. KRAS status was assessed also in matched adenocarcinoma and HGIN tissues. The distribution of cfDNA concentrations among FOBT-positive subjects with diag nosed lesion (cases) was compared with that of FOBT-positive subjects without le sions (controls) and its predictive capability (AUC) was assessed. Results . The predictive capability of cfDNA levels was satisfactory in predicting ade nocarcinomas (AUC 0.709; 95% CI, 0.508-0.909) but not HGIN and premalignant le sions. The rate of KRAS mutations in plasma was low (5/170 = 3%) compared with the rate observed in the matched adenocarcinoma and HGIN tissues (45%). Conclusions . The use of cfDNA quantification to predict adenocarcinoma at an early stage in high-risk (aged >50 years and FOBT positive) subjects seems to be promising