Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Cancer Chemother Pharmacol. 2020 Apr;85(4):785-792. doi: 10.1007/s00280-020-04053-9. Epub 2020 Mar 19.
Capecitabine is a widely used 5-fluorouracil oral prodrug. Hand-foot syndrome (HFS), one of the most common adverse events of capecitabine, impacts patients' quality of life seriously. The pathogenesis of HFS remains unclear but was usually considered as a type of inflammation conducted by cyclooxygenase-2 (COX-2). The COX-2/PGES/EP signaling pathway plays an important role in the inflammatory reaction. We hypothesized that the single nucleotide polymorphisms (SNPs) in this pathway may be associated with the risk of HFS induced by capecitabine.
Using DNA from blood samples of 225 patients, we genotyped 19 SNPs in 6 core genes (COX-2, PGES, EP1, EP2, EP3, and EP4). Common Terminology Criteria for Adverse Events version 3.0 was used to grade hand-foot syndrome. We used logistic regression analysis to evaluate the correlations between genotype variants and occurrence of HFS. The cumulative incidence of HFS was assessed by Kaplan-Meier analysis.
Among the 225 participants, 58.6% (132/225) patients developed into HFS, including 41.3% (93/225) grade 1 HFS, 10.2% (23/225) grade 2 HFS and 7.1% (16/225) grade 3 HFS. Multivariate logistic regression analysis showed the AG/GG genotype of rs3810255 to be associated with a significantly higher risk of grade 2/3 HFS, while the AG/AA genotype of rs17131450 to be associated with a significantly lower risk of grade 2/3 HFS (OR = 3.646, P = 0.011; and OR = 0.266, P = 0.036; respectively).
Our study showed that rs3810255 AG/GG genotypes and rs17131450 GG genotypes to be associated with high risk of capecitabine-induced HFS.
卡培他滨是一种广泛应用的 5-氟尿嘧啶口服前体药物。手足综合征（HFS）是卡培他滨最常见的不良反应之一，严重影响患者的生活质量。HFS 的发病机制尚不清楚，但通常被认为是一种由环氧化酶-2（COX-2）介导的炎症。COX-2/PGES/EP 信号通路在炎症反应中起重要作用。我们假设该通路中的单核苷酸多态性（SNP）可能与卡培他滨引起的 HFS 风险相关。
使用来自 225 名患者的血液样本中的 DNA，我们对 6 个核心基因（COX-2、PGES、EP1、EP2、EP3 和 EP4）中的 19 个 SNP 进行了基因分型。采用常见不良事件术语标准 3.0 对 HFS 进行分级。我们使用逻辑回归分析评估基因型变异与 HFS 发生之间的相关性。通过 Kaplan-Meier 分析评估 HFS 的累积发生率。
在 225 名参与者中，58.6%（132/225）的患者发生 HFS，包括 41.3%（93/225）的 1 级 HFS、10.2%（23/225）的 2 级 HFS 和 7.1%（16/225）的 3 级 HFS。多变量逻辑回归分析显示 rs3810255 的 AG/GG 基因型与 2/3 级 HFS 的发生风险显著相关，而 rs17131450 的 AG/AA 基因型与 2/3 级 HFS 的发生风险显著相关（OR=3.646，P=0.011；和 OR=0.266，P=0.036）。
我们的研究表明，rs3810255 的 AG/GG 基因型和 rs17131450 的 GG 基因型与卡培他滨引起的 HFS 风险增加相关。
