Bridging Lipids and Colon Cancer: The Mediating Influence of Inflammation

Background : Colon cancer(CC) is a common and deadly cancer. Research indicates a connection between inflammation, lipids, and colon cancer, though the precise nature of this relationship remains uncertain. Method : We performed a two-sample Mendelian randomization(MR) analysis to examine the potential mediating role of inflammation in the relationship between lipids and colon cancer. In this study, we utilized recently published genome-wide association study (GWAS) data pertaining to lipids, inflammation, and colon cancer. The GeneRISK cohort provided lipid GWAS data from 7,169 Finnish individuals of European ancestry. Inflammation GWAS data were collected from 14,824 European participants across 11 cohorts using the Olink Target Inflammation panel. Colon cancer GWAS data were sourced from the IEU GWAS catalog (UKB-B-20145). Results : In this study, we identified onemediating relationship between inflammation, lipid, and colon cancer. Specifically, Phosphatidylethanolamine(PE) was found to indirectly influence colon cancer via Axin-1 concentration (OR=0.88 [95%CI(0.78, 0.99)], P =0.04).Although no mediating role of IL-17 in the relationship between phosphatidylcholine(PC) and CC was observed, our results suggest that PC can promote the development of CC(OR=1.12 [95%CI(1.00,1.24)], P=0.040), while IL-17 can inhibit the progression of CC(OR=0.87 [95%CI(0.76, 0.99)], P=0.034). Discussion : In conclusion, our MR analysis identifies the indirect effects of and Axin1 on the PE to CC, supporting the link between genetically predicted lipid levels, inflammation, and CC. These findings furnish genetic evidence that underscores the role of lipid and inflammation mechanisms in reducing the risk of CC, thereby providing valuable insights for future mechanistic and clinical research.