遗传因素与结直肠癌（CRC）生存之间的关联研究有限且不一致，并揭示其预后作用的机制具有重要意义。本研究旨在探讨功能性遗传变异与CRC预后之间的关系，并进一步揭示可能的机制。我们首先采用The Cancer Genome Atlas（TCGA）数据集系统地进行表达定量性状座位（eQTL）分析。然后，使用Kaplan-Meier分析从TCGA和来自Gene Expression Omnibus数据库的GSE39582数据集中筛选出与CRC患者生存相关的eQTL靶基因。将与七个生存相关的eQTL靶基因关联的最有潜力的六个生存相关eQTL单核苷酸多态性（SNP）在907名中国CRC患者中进行基因分型，并附有临床预后数据。功能实验证实了与生存相关的SNP的调控机制。调控内质网氨肽酶1（ERAP1）表达的rs71630754与CRC预后显著相关（加性模型，风险比[HR]：1.43，95%置信区间[CI]：1.08-1.88，P = 0.012）。双荧光素酶报告基因实验和电泳迁移法实验结果显示，rs71630754的A等位基因可以增加转录因子3（TCF3）的结合，从而降低ERAP1的表达。生物信息学分析结果显示，ERAP1的较低表达会影响肿瘤免疫微环境，并与严重的预后结果显著相关。rs71630754通过调控与免疫相关的基因ERAP1的表达可能影响CRC患者的预后。版权所有© 2023中国医学协会，由Wolters Kluwer, Inc.根据CC-BY-NC-ND许可证制作。

Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 (ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and be significantly associated with severe survival outcomes.The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1.Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.