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

Several studies reported the sterol ester (SE), a subclass of subtype of cholesterol ester (CE), is associated with the incidence of colorectal cancer (CRC). Nevertheless, the causal relationship of SE on CRC remains unknown.

A two-sample Mendelian randomization study was performed with the summary statistics of SE (27:1/14:0) which is 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 a relative relaxed filter (p < 5 × 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 × 10^- 8 and LD r² < 0.01, MR Egger intercept, MR-PRESSO, and leave-one-out method, which all support the causal assessment. 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.

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 model. However, 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 results of MR analysis were not driven by a single SNP. And results from two filter threshold is consistent.

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.