Plasma Protein Biomarkers for Early Risk Prediction of Colorectal Cancer.

Abstract

Background: Prospective studies are necessary to determine the association between circulating proteins and colorectal cancer risk, offering noninvasive biomarkers for early colorectal cancer risk prediction and interventions.

Methods: The Olink Explore 3072 platform was employed to measure 2,923 plasma proteins in 53,073 UK Biobank participants. Cox regression analyses assessed associations between normalized protein expression and colorectal cancer risk. We developed a protein score for colorectal cancer risk prediction and compared it with a traditional risk model (incorporating age, sex, body mass index, smoking status, alcohol consumption, physical activity, and family history of colorectal cancer) using receiver operating characteristic analysis.

Results: Over an average 10.8-year follow-up, 652 colorectal cancer cases occurred. After multivariable adjustment, seven proteins showed significant associations with colorectal cancer risk (false discovery rate-corrected P values < 0.05). Hazard ratios (HR) for colorectal cancer per one standard deviation increase in levels of these proteins ranged from 1.18 [95% confidence interval (CI), 1.07-1.29] to 1.38 (95% CI, 1.23-1.55). Compared with the lowest quintile, the highest quintile of the seven-protein score was associated with an HR for colorectal cancer of 4.27 (95% CI, 3.17-5.75). The protein score model and traditional risk factor model showed similar predictive performance for 5-year colorectal cancer risk [both areas under the curve (AUC) = 0.68], whereas the combined model showed an AUC of 0.70.

Conclusions: This study established a panel of seven plasma proteins that may help identify high-risk individuals for colorectal cancer.

Impact: This study highlights the potential of plasma protein biomarkers as noninvasive tools for early detection and personalized prevention strategies of colorectal cancer.