The chemotherapeutic efficacy in colorectal cancer (CRC) is limited due to the inter-individual variability in drug response and the development of tumour resistance. ATP-binding cassette (ABC) transporters are crucial in the development of resistance by the efflux of anticancer agents from cancer cells. In this study, we identified 14 single nucleotide polymorphisms (SNPs) in 11 ABC transporter genes acting as an expression of quantitative trait loci (eQTLs), i.e. whose variation influence the expression of many downstream genes. These SNPs were genotyped in a case–control study comprising 1098 cases and 1442 healthy controls and analysed in relation to CRC development risk and patient survival. Considering a strict correction for multiple tests, we did not observe any significant association between SNPs and CRC risk. The rs3819720 polymorphism in the ABCB3/TAP2 gene was statistically significantly associated with shorter overall survival (OS) in the codominant, and dominant models [GA vs. GG, hazard ratio (HR) = 1.48; P = 0.002; AA vs. GG, HR = 1.70; P = 0.004 and GA + AA vs. GG, HR = 1.52; P = 0.0006]. Additionally, GA carriers of the same SNP displayed worse OS after receiving 5-FU based chemotherapy. The variant allele of rs3819720 polymorphism statistically significantly affected the expression of 36 downstream genes. Screening for eQTL polymorphisms in relevant genes such as ABC transporters that can regulate the expression of several other genes may help to identify the genetic background involved in the individual response to the treatment of CRC patients.

中文翻译：

---

ABC转运蛋白中的表达数量性状基因座与5-FU治疗的大肠癌患者的生存相关。

由于个体间药物反应的差异和肿瘤耐药性的发展，结直肠癌（CRC）的化学治疗功效受到限制。ATP结合盒（ABC）转运蛋白通过癌细胞中抗癌剂的外流在耐药性发展中至关重要。在这项研究中，我们确定了11个ABC中的14个单核苷酸多态性（SNP）转运蛋白基因充当定量性状基因座（eQTL）的表达，即其变异影响许多下游基因的表达。在一项包括1098例病例和1442例健康对照的病例对照研究中，对这些SNP进行了基因分型，并就CRC发生风险和患者生存率进行了分析。考虑到多项测试的严格校正，我们未发现SNP与CRC风险之间有任何显着关联。统计学上，ABCB3 / TAP2基因中的rs3819720多态性与显性和显性模型的总体生存期较短（OS）显着相关[GA vs. GG，风险比（HR）= 1.48；P  = 0.002; AA vs.GG，HR = 1.70; P  = 0.004，GA + AA vs. GG，HR = 1.52；P = 0.0006]。此外，具有相同SNP的GA携带者在接受基于5-FU的化疗后，其OS恶化。rs3819720多态性的变异等位基因在统计学上显着影响36个下游基因的表达。在相关基因（例如可以调节其他几个基因表达的ABC转运蛋白）中筛选eQTL多态性，可能有助于鉴定涉及对CRC患者的个体反应的遗传背景。