Department of General Surgery, The Ganzhou People's Hospital, 18 Meiguan Avenue, Ganzhou, Jiangxi, China.
Department of Ultrasound, The First Affiliated Hospital of University of South China, No.69, Chuanshan Road, Shigu District, Hengyang, Hunan, 421000, China.
BMC Cancer. 2024 Nov 27;24(1):1462. doi: 10.1186/s12885-024-13228-z.
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 and LD r < 0.01) of instrumental variables to explore the causal effect and complete the sensitive analysis with the threshold p < 5 × 10 and LD r < 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.
几项研究报告称，甾醇酯（SE）是胆固醇酯（CE）的一个亚类，与结直肠癌（CRC）的发病率有关。然而，SE 对 CRC 的因果关系尚不清楚。
采用 FinnGen 联盟进行的最大全基因组关联研究荟萃分析的汇总统计数据（SE（27:1/14:0）进行两样本 Mendelian 随机化研究（n=377277）。汇总数据来自英国生物银行数据库（377673 例病例和 372016 例对照）。我们使用相对宽松的工具变量（p<5×10 和 LD r<0.01）来探索因果效应，并使用阈值 p<5×10 和 LD r<0.01、MR Egger 截距、MR-PRESSO 和单样本剔除法完成敏感分析，所有这些方法都支持因果评估。逆方差加权、MR-Egger、加权中位数、简单模式和加权模型用于检验 SE（27:1/14:0）与 CRC 之间的因果关联。 Cochran's Q 统计量用于量化工具变量的异质性。
IVW 结果表明，SE（27:1/14:0）（OR=1.004；95%CI 1.002，1.005；p<0.001）与 CRC 具有遗传因果关系。加权中位数、加权模式和简单模式的结果均与 IVW 模型一致。然而，MR-Egger 方法的结果（OR=1.005；95%CI 1.004，1.009；p=0.052）并未显示出显著结果。没有异质性、水平偏倚或异常值，且结果呈正态分布。MR 分析的结果不受单个 SNP 的驱动。并且两种过滤阈值的结果一致。
总的来说，遗传预测的甾醇酯（27:1/14:0）在 CRC 的发病中起因果关系作用。这一发现将为未来 CRC 的筛查和诊断提供一个新的指标。
