Abstract
Simple SummaryCurrently, colorectal cancer screening typically involves stool tests, but a blood test might be more acceptable for screening participants. Most research on blood biomarkers for colorectal cancer has been conducted using samples from patients and may not be as predictive for early-stage cancer or pre-cancerous tumors. This systematic review summarizes the evidence from studies that used samples collected before the onset of symptoms. The quality of the studies was generally high, but very few potential biomarkers showed consistent, clinically relevant results across more than one study. Of these, the anti-p53 antibody was the most promising marker. Panels of biomarkers performed better than single markers. The results of this review underscore the need for validation of promising colorectal cancer biomarkers in independent pre-diagnostic settings.This systematic review summarizes the evidence for blood-based colorectal cancer biomarkers from studies conducted in pre-diagnostic, asymptomatic settings. Of 1372 studies initially identified, the final selection included 30 studies from prospective cohorts and 23 studies from general screening settings. Overall, the investigations had high quality but considerable variability in data analysis and presentation of results, and few biomarkers demonstrated a clinically relevant discriminatory ability. One of the most promising biomarkers was the anti-p53 antibody, with consistent findings in one screening cohort and in the 3–4 years prior to diagnosis in two prospective cohort studies. Proteins were the most common type of biomarker assessed, particularly carcinoembryonic antigen (CEA) and C-reactive protein (CRP), with modest results. Other potentially promising biomarkers included proteins, such as AREG, MIC-1/GDF15, LRG1 and FGF-21, metabolites and/or metabolite profiles, non-coding RNAs and DNA methylation, as well as re-purposed routine lab tests, such as ferritin and the triglyceride–glucose index. Biomarker panels generally achieved higher discriminatory performance than single markers. In conclusion, this systematic review highlighted anti-p53 antibodies as a promising blood-based biomarker for use in colorectal cancer screening panels, together with other specific proteins. It also underscores the need for validation of promising biomarkers in independent pre-diagnostic settings.
Highlights
Introduction conditions of the Creative CommonsColorectal cancer is the second most common cancer in men and women globally [1], affecting roughly one in twenty people over the course of their lifetime
The most common reason for excluding an abstract was the use of post-diagnostic blood samples (n = 139)
Several studies used an approach focused on risk and etiology, with no clear intent to identify or validate biomarkers from the perspective of risk prediction or early detection (n = 59) or had an unclear or irrelevant study setting (n = 34), which was confirmed by a specific check of the methods section of the full paper when the independent author assessments were incongruent
Summary
Colorectal cancer is the second most common cancer in men and women globally [1], affecting roughly one in twenty people over the course of their lifetime. A disease of older age, colorectal cancer incidence rates can be expected to rise as life expectancy. Increases in a population, but trends have been reversed in some countries, including the United States [2], largely due to the implementation of age-based general screening programs [3]. The gold standard for colorectal cancer screening is full colonoscopy. In addition to providing the best chance of detecting colorectal cancer through, ideally, inspection of the entire colorectal epithelium, colonoscopy has important advantages as a screening technique. A tool for early detection of asymptomatic colorectal cancer, and for primary prevention. The implementation of colonoscopy for general screening is limited by several factors. Achieving adequate uptake is a challenge, which is further hampered by inabilities to adequately capture all socioeconomic and ethnic groups [4]
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