The association of ABCC5 and ABCC11 polymorphisms with the pharmacokinetics of 5-FU in advanced gastric cancer patients

Year 2020, Volume: 10 Issue: 3, 285 - 291, 29.09.2020

Zeliha Pala Kara , Ezgi Oztas Dilek Ozturk , Yasemin Akyel Zeynep Turna , Alper Okyar Gül Özhan

https://doi.org/10.33808/clinexphealthsci.757619

Abstract

Objective: Gastric cancer is the second leading cause of cancer-related death worldwide. 5-Fluorouracil (5-FU) is one of the most commonly used drugs to treat cancer, but 5-FU and its forms are characterized by wide inter-individual pharmacokinetic variability. ABCC5 and ABCC11 are members of the ABC transporter superfamily and play a role in the efflux of antineoplastic drugs like 5-FU.
Methods: The influence of two SNPs in ABCC5 (rs562, T>C) and ABCC11 (rs17822931, G>A) was evaluated based on the pharmacokinetics and toxicity of 5-FU in HER2-negative advanced gastric cancer patients treated with cisplatin and 5-FU (n=18). The genetic variants and plasma 5-FU concentrations were detected by RT-PCR and HPLC, respectively.
Results: There was no statistically significant difference between 5-FU AUC0-96 h values and ABCC5 (rs562; T>C), 21.04 ±3.46 vs 16.65 μg.h/mL, p=0,261) and ABCC11 (rs17822931; G>A), 17.04 ±4.39 vs 54 ±3.79 mg.h/L, p=0,564) variants. Similarly, there were no statistically significant differences between the variants and the most frequently observed side effects of diarrhea and mucositis.
Conclusion: We recommend investigating the noted SNPs more precisely in a larger study population with more comprehensive evaluation.

Keywords

ABCC5, ABCC11, 5-FU, Pharmacogenetics, Gastric cancer

Supporting Institution

Scientific Research Projects Coordination Unit of Istanbul University

Project Number

25139 and 24985

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