The Association between ATP-Binding Cassette C2 (ABCC2) Transporter Genetic Polymorphism and Peripheral Neuropathy in Gastrointestinal Cancer Patients Receiving Oxaliplatin.

Sara Abdel Aziz, Diaa Eldin Sherif, Nagwa Sabri, May Shawki
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Abstract

Single nucleotide polymorphisms (SNPs) in the ATP-binding cassette C2 (ABCC2) gene increased intracellular oxaliplatin accumulation in the dorsal root ganglia may result in an increased risk of oxaliplatin-induced peripheral neuropathy (OXAIPN). The present study aims to study the association between the SNPs rs1885301 G>A, rs4148396 C>T, and rs3740066 C>T in the ABCC2 gene and the incidence of OXAIPN in gastrointestinal cancer patients. The study was a prospective cohort study carried out at the Clinical Oncology Department, Ain Shams University Hospitals. Eligible patients received FOLFOX6 and FOLFIRINOX for 8-12 cycles. The SNPs assessment was performed using Real-time PCR using the Rotor gene Q (QIAGEN ® ) system. The patients were followed up with each cycle to assess the incidence and severity of OXAIPN and other common toxicities including diarrhea, vomiting, and neutropenia. One hundred and twenty patients were included in the study. The minor allele frequency for the SNPs rs1885301 G>A, rs4148396 C>T, and rs3740066 C>T were 0.4-0.2, and 0.3 respectively. The current study showed no association between the three SNPs and the incidence and grade of OXAIPN with less than 50% of the participants reporting grade III and IV peripheral neuropathy. A significant association was found between rs4148396 C>T and the occurrence of neutropenia where TT haplotype showed a significantly higher incidence of neutropenia compared to CC + CT. In conclusion, no association was found between the SNPs and the occurrence of PN, diarrhea, and vomiting. There was only a significant difference in the incidence grades of neutropenia among haplotypes of rs4148396 C>T.
接受奥沙利铂治疗的胃肠道癌症患者的 ATP 结合盒 C2 (ABCC2) 转运体基因多态性与周围神经病变之间的关系
ATP结合盒C2(ABCC2)基因中的单核苷酸多态性(SNPs)增加了细胞内奥沙利铂在背根神经节中的蓄积,可能导致奥沙利铂诱导的周围神经病变(OXAIPN)风险增加。本研究旨在探讨 ABCC2 基因中的 SNPs rs1885301 G>A、rs4148396 C>T 和 rs3740066 C>T 与胃肠道癌症患者 OXAIPN 发病率之间的关联。该研究是一项前瞻性队列研究,在艾因夏姆斯大学医院临床肿瘤科进行。符合条件的患者接受了 8-12 个周期的 FOLFOX6 和 FOLFIRINOX 治疗。SNPs 评估采用 Rotor gene Q (QIAGEN ® ) 实时 PCR 系统进行。每个周期对患者进行随访,以评估 OXAIPN 及其他常见毒性反应(包括腹泻、呕吐和中性粒细胞减少症)的发生率和严重程度。研究共纳入了 120 名患者。SNP rs1885301 G>A、rs4148396 C>T和rs3740066 C>T的小等位基因频率分别为0.4-0.2和0.3。目前的研究显示,这三个 SNP 与 OXAIPN 的发病率和等级没有关系,只有不到 50% 的参与者报告了 III 级和 IV 级周围神经病变。研究发现,rs4148396 C>T 与中性粒细胞减少症的发生有明显关联,其中 TT 单倍型与 CC + CT 相比,中性粒细胞减少症的发生率明显更高。总之,SNPs 与中性粒细胞减少症、腹泻和呕吐的发生没有关联。只有在 rs4148396 C>T 的单倍型中,中性粒细胞减少症的发病率等级有明显差异。
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