Effect of Polymorphisms in Drug Transporters on Cisplatin Efficacy and Nephrotoxicity in Paediatric Osteosarcoma

Abstract

Introduction: Osteosarcoma (OS) is the most common type of primary bone tumor in children and adolescents. Chemotherapeutic resistance to cisplatin represents such a significant barrier in the successful treatment of Osteosarcoma. The degree of nephrotoxicity and drug resistance (poor tumor necrosis) is associated with cisplatin accumulation in cells which is governed by Copper transporter protein 1 (CTR1) and Organic cation transporter 2 (OCT2). This study aims to determine the allelic frequency of CTR1 and OCT2 single nucleotide polymorphisms (SNPs) in osteosarcoma patients. In addition, detect the relation between SNPs in transporters and cisplatin efficacy or nephrotoxicity.
 Methods: A group of 120 pediatric osteosarcoma patients was recruited and genotyped for CTR1, rs7851395, and OCT2 rs316019. We detected the allelic frequency of the two gene polymorphisms. We defined good responders versus poor responders depending on tumor necrosis parameters and looked at nephrotoxicity and serum electrolytes according to CTCAEv4 using the Chi-square test (c2) and Kruskal-Wallis value, the odds ratio and confidence interval were calculated too.
 Results: We found that the C allele in (rs316019) OCT2 polymorphism was the dominant allele, and patients with (C/C genotype) were the dominant genotype (72%). and the "A" allele is the dominant allele in (rs7851395) CTR1 and patients with (A/A genotype) were (39.5%).
 Conclusion: the study had found that the "C" allele is the dominant allele in (rs316019) OCT2 and the "A" allele is the dominant allele in (rs7851395) CTR1, the study didn't find any significant relation between CTR1, OCT2 polymorphisms and cisplatin response or nephrotoxicity and farther multi center studies need to be done.