The association between genetically predicted C-reactive protein levels and risk of colorectal cancer in an East Asian population: two-sample Mendelian randomization

Background: C-reactive protein (CRP) is a widely used inflammatory biomarker that has been related to colorectal cancer (CRC) risk. However, observational studies are prone to confounding and reverse causality. Methods: We conducted a two-sample Mendelian randomization using CRP GWAS data from 59,605 Korean individuals and CRC GWAS data from 23,572 cases and 48,700 controls from an East Asia population. The analysis had 80% power to detect an odds ratio (OR) of 1.12 for CRC risk per two-fold increase in CRP levels. Results: Genetically predicted serum CRP levels (per two-fold increase) were not significantly associated with CRC 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 CRC 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.