Irinotecan治疗的副作用可能限制剂量并影响生活质量。本研究探讨了除UGT1A1外，参与irinotecan代谢和转运的酶基因中的单核苷酸多态性（SNPs）与irinotecan相关毒性之间的相关性。我们关注的是参与活性代谢物SN-38形成的羧酯酶和药物转运蛋白。符合Erasmus医学中心肿瘤学院Code Geno研究（本地方案：MEC02-1002）或IRI28研究（NTR-6612）的入组患者提供了书面知情同意，并对CES1、CES2、SLCO1B1、ABCB1、ABCC2和ABCG2基因中的15个SNPs进行了基因分型。从299名可评估患者中，86名患者（28.8%）出现了严重的irinotecan相关毒性。ABCG2 c.421C>A变异等位基因携带者的毒性风险显著增加（P = 0.030，OR 1.88，95% CI 1.06-3.34）。年龄较大与所有级别的腹泻有关（P = 0.041，OR 1.03，95% CI 1.00-1.06）。此外，CES1 c.1165-41C>T和CES1 n.95346T>C变异等位基因携带者患有全级别血小板减少的风险较低（P = 0.024，OR 0.42，95% CI 0.20-0.90和P = 0.018，OR 0.23，95% CI 0.08-0.79）。我们的研究表明，ABCG2和CES1 SNPs可能用作irinotecan引起的毒性的预测标志物。© 2023. 作者。

Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the irinotecan metabolism and transport, outside UGT1A1, and irinotecan-related toxicity. We focused on carboxylesterases, which are involved in formation of the active metabolite SN-38 and on drug transporters.Patients who provided written informed consent at the Erasmus Medical Center Cancer Institute to the Code Geno study (local protocol: MEC02-1002) or the IRI28-study (NTR-6612) were enrolled in the study and were genotyped for 15 SNPs in the genes CES1, CES2, SLCO1B1, ABCB1, ABCC2, and ABCG2.From 299 evaluable patients, 86 patients (28.8%) developed severe irinotecan-related toxicity. A significantly higher risk of toxicity was seen in ABCG2 c.421C>A variant allele carriers (P = 0.030, OR 1.88, 95% CI 1.06-3.34). Higher age was associated with all grade diarrhea (P = 0.041, OR 1.03, 95% CI 1.00-1.06). In addition, CES1 c.1165-41C>T and CES1 n.95346T>C variant allele carriers had a lower risk of all-grade thrombocytopenia (P = 0.024, OR 0.42, 95% CI 0.20-0.90 and P = 0.018, OR 0.23, 95% CI 0.08-0.79, respectively).Our study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.© 2023. The Author(s).