Unraveling the link between sterol ester and colorectal cancer: a two-sample Mendelian randomization study

Abstract

Background Several studies reported the sterol ester (SE), one subclass of subtype of cholesterol esters (CE), is associated with the incidence of Colorectal cancer (CRC). Nevertheless, the causal relationship of SE on CRC remains unknown. Methods A two-sample Mendelian randomization study was performed with the summary statistics of sterol ester (27:1/14:0) from the largest available genome-wide association study meta-analysis(n = 377277) conducted by FinnGen consortium. The summary data were obtained from UK Biobank repository (377673 cases and 372016 controls). And we used relative filter (p < 5 x 10^− 6 and LD r² < 0.01) of instrumental variables to explore the causal effect and complete the sensitive analysis with the threshold p < 5 x 10^− 8 and LD r² < 0.01. Inverse variance weighted, MR-Egger, weighted median, Simple Mode and weighted model, were used to examine the causal association between SE (27:1/14:0) and CRC. Cochran’s Q statistics were used to quantify the heterogeneity of instrumental variables. Results The IVW results showed that SE (27:1/14:0) (OR = 1.004; 95% CI 1.002, 1.005; p < 0.001) have genetic causal relationship with CRC. The results of Weighted median, Weighted mode and Simple mode are all consistent with IVW models. Though, the result from the MR-Egger method (OR = 1.005; 95% CI 1.004, 1.009; p = 0.052) didn’t demonstrate a significant result. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The MR analysis results were not driven by a single SNP. And results from two filter threshold is consistent. Conclusion Altogether, genetically predicted sterol ester (27:1/14:0) plays a causal association role in the incidence of CRC. This finding will provide a new screening and diagnosis indicator of CRC in the future.