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

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.