Colorectal cancer detected by liquid biopsy 2 years prior to clinical diagnosis in the HUNT study

BACKGROUND: Colorectal cancer (CRC) is often diagnosed in advanced stages. Circulating tumour DNA (ctDNA) has been proposed as an early diagnostic biomarker, but most screening studies assess selected populations at diagnosis. Aim: detect CRC by known ctDNA methylation markers up to 2 years before clinical diagnosis. METHODS: In a case–control study, methylated ctDNA markers were measured in plasma from 106 healthy controls and 106 individuals who developed CRC within 24 months after participation in the Trøndelag Health Study. The most specific single markers were BMP3, FLT1, IKZF1, SFRP1, SFRP2, NPTX2, SLCA1 and VIM (specificity >70%). A combined panel achieved 43% sensitivity (95% CI 42.7–43.4) and 86% specificity (95% CI 85.7–86.2). Results were reproduced in an independent validation set. CONCLUSIONS: Known methylated ctDNA CRC markers are detectable up to 2 years prior to diagnosis in an unselected, screening-like population, supporting the potential of ctDNA detection to enable earlier CRC diagnosis if implemented in screening.

Siv S. Brenne, Poul Henning Madsen, Inge Søkilde Pedersen, Kristian Hveem, Frank Skorpen, Henrik Bysum Kaurup, Guro F. Giskeødegård, Eivor A. Lausgård