The Association between Genetically Predicted C-Reactive Protein Levels and Risk of Colorectal Cancer in an East Asian Population: Two-Sample Mendelian Randomization

Abstract

Background: C-reactive protein (CRP) is a widely used inflammatory biomarker that has been related to colorectal cancer risk. However, observational studies are prone to confounding and reverse causality.Methods: We conducted a two-sample Mendelian randomization using CRP genome-wide association study (GWAS) data from 59,605 Korean individuals and colorectal cancer GWAS data from 23,572 cases and 48,700 controls from an East Asia population. The analysis had 80% power to detect an OR of 1.12 for colorectal cancer risk per twofold increase in CRP levels.Results: Genetically predicted serum CRP levels (per twofold increase) were not significantly associated with colorectal cancer risk (inverse-variance weighted OR, 0.995; 95% confidence interval, 0.893-1.109; P value, 0.929). Null findings remained consistent in sensitivity analyses excluding the horizontally pleiotropic effect.Conclusions: Despite sufficient statistical power, little evidence supported a causal association between CRP and colorectal cancer risk in East Asians.Impact: Our findings suggest that CRP is unlikely to be a key determinant of colorectal carcinogenesis, aligning with prior studies in European populations.