Association of Genetic Polymorphism of ABCG2 Gene and the Occurrence of Oxaliplatin-Induced Peripheral Neuropathy in Patients with Colorectal Cancer

Ahmed, Inas M. M.; El Wakeel, Lamia M.; Saad, Amr S.; Emam, Ahmed A.; Abdel-Malek, Raafat R.; Abdel Wahab, Abdel Hady A.

doi:10.21608/aps.2023.232727.1137

Association of Genetic Polymorphism of ABCG2 Gene and the Occurrence of Oxaliplatin-Induced Peripheral Neuropathy in Patients with Colorectal Cancer

Document Type : Original Article

Authors

¹ Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.

² Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

³ Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt.

⁴ Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt.

10.21608/aps.2023.232727.1137

Abstract

Background: Oxaliplatin use in gastrointestinal malignancies is limited by neurotoxicity. This study aims to identify single-nucleotide polymorphisms (SNPs) in the ABCG2 gene associated with oxaliplatin-induced peripheral neuropathy (OIPN) in Egyptian Colorectal Cancer (CRC) patients treated with oxaliplatin-based chemotherapy (CT).
Patients and methods: All eligible CRC patients between the ages of 18 and 80 participated in the study, and those with a neurological illness or condition limiting neurologic function were excluded. On the first day of every CT cycle, OIPN was assessed and scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v.4. Blood was utilized to extract genomic DNA in order to detect SNPs in the ABCG2 gene (at rs2231137and at rs3114018) using High Resolution Melting (HRM) technique followed by direct sequencing method for every melting cluster using 3500 genetic analyzers for the samples selected from each cluster.
Results: The occurrence of grade 2-3 OIPN was higher in patients carrying the G/G genotype of ABCG2 (rs2231137) than those with G/A genotype at the same locus (rs2231137) (96.7% versus 82.0%; P=0.05). While, grade 2-3 OIPN occurrence was not significantly different in patients carrying genotypes (C/C, A/C, and A/A) of ABCG2 at rs3114018 (92.9%, 82.1% and 80.0% respectively; P=0.309).
Conclusion: The occurrence of OIPN among Egyptian Colorectal Cancer (CRC) patients was more associated with the G/G allele genotype of ABCG2 (rs2231137). While, patients carrying different genotypes (C/C, A/C, and A/A) of ABCG2 at rs3114018 were similarly associated with OIPN in this patient population.

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