Purpose Methylated cell-free DNA in liquid biopsies are promising non-invasive biomarkers for colorectal cancer (CRC). Optimal markers would have high sensitivity and specificity for early detection of CRC and could be detected in more than one type of material from the patient. We systematically reviewed the literature on DNA methylation markers of colorectal cancer, detected in more than one type of material, regarding their potential as contributors to a panel for screening and follow-up of CRC. Methods The databases MEDLINE, Web of Science, and Embase were systematically searched. Data extraction and review was performed by two authors independently. Agreement between methylation status in tissue and other materials (blood/stool/urine) was analyzed using the McNemar test and Cohen’s kappa. Results From the 51 included studies, we identified seven single markers with sensitivity ≥ 75% and specificity ≥ 90% for CRC. We also identified one promising plasma panel and two stool panels. The correspondence of methylation status was evaluated as very good for four markers, but only marginal for most of the other markers investigated (12 of 21). Conclusion The included studies reported only some of the variables and markers of interest and included few patients. Hence, a meta-analysis was not possible at this point. Larger, prospective studies must be designed to study the discordant detection of markers in tissue and liquid biopsies. When reporting their findings, such studies should use a standardized format.

Background Colorectal cancer (CRC) is often diagnosed in advanced stages. Circulating tumour DNA (ctDNA) has been proposed as an early diagnostic biomarker. However, as a screening tool, ctDNA has mainly been studied in selected populations at the time of clinical diagnosis. The aim of this study was to detect CRC by known ctDNA markers up to 2 years prior to clinical diagnosis. Methods In this case–control study, methylated ctDNA markers were detected in plasma samples from 106 healthy controls and 106 individuals diagnosed with CRC within 24 months following participation in The Trøndelag Health Study. Results The most specific single markers were BMP3, FLI1, IKZF1, SFRP1, SFRP2, NPTX2, SLC8A1 and VIM (specificity >70%). When combining these into a panel, the CRC sensitivity was 43% (95% CI 42.7–43.4) and the CRC specificity was 86% (95% CI 85.7–86.2). The findings were reproduced in an independent validation set of samples. Conclusions Detection of known methylated ctDNA markers of CRC is possible up to 2 years prior to the clinical diagnosis in an unselected population resembling the screening setting. This study supports the hypothesis that some patients could be diagnosed earlier, if ctDNA detection was part of the CRC screening programme.

Aim The aim of this study was to assess established risk factors for colorectal cancer (CRC) separately for right colon, left colon and rectal cancer in men and women. Method This was a prospective cohort study comparing incidental CRC cases and the general population participating in a longitudinal health study in Norway (the HUNT study). Results Among 78 580 participants (36 825 men and 41 754 women), 1827 incidental CRCs were registered (931 men and 896 women). Among men, the risk of cancer at all locations increased with age [HR 1.46 (1.40–1.51), HR 1.32 (1.27–1.36), HR 1.30 (1.25–1.34) per 5 years for right colon, left colon and rectal cancer, respectively] and the risk of left colon cancer increased with higher body mass index [HR 1.28 (1.12–1.46) per 5 kg/m2]. The risk of right colon cancer (RCC) increased with smoking [HR 1.07 (1.04–1.10) per 5 pack years]. Among women, the risk of cancer at all locations increased with age [HR 1.38 (1.34–1.43), HR 1.23 (1.19–1.27), HR 1.20 (1.16–1.24) per 5 years] and smoking [HR 1.07 (1.02–1.12), HR 1.07 (1.02–1.12), HR 1.10 (1.05–1.17) per 5 pack years] for right colon, left colon and rectal cancer, respectively. The risk of RCC increased with night shift work [HR 1.93 (1.22–3.05)]. Conclusion The risk factors for developing CRC differ by anatomical location and sex. The relationship between risk factors and CRC may be more nuanced than previously known.