Relationship Between High-Density Lipoprotein Cholesterol and Colorectal Cancer—A Mendelian Randomization Study

ObjectiveTo elucidate the causal relationship between high-density lipoprotein cholesterol (HDL-C) and colorectal cancer (CRC) through Mendelian randomization. MethodsMendelian randomization analysis was conducted using genetic instrumental variables selected from a genome-wide association study dataset. The main methods included inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode method; among which, inverse variance weighted method served as the primary analytical approach. Sensitivity analyses were performed to verify the robustness of results. ResultsA total of 41 genetic instrumental variables associated with HDL-C were identified. Inverse variance weighted method (OR=0.84, 95%CI: 0.73-0.96, P=0.01) and weighted median method (OR=0.82, 95%CI: 0.67-0.99, P=0.04) indicated a negative correlation between genetically-determined HDL-C and CRC risk. Sensitivity analyses confirmed the absence of heterogeneity and horizontal pleiotropy (P>0.05). ConclusionA causal relationship exists between HDL-C and CRC risk, with rs1077834 as a potential key determinant in the influence of HDL-C on CRC risk.