Polymorphisms in Slco1B3 and Nr1I2 as Genetic Determinants of Hematotoxicity of Carboplatin and Paclitaxel Combination

Abstract

Aim: The goal of our study was to assess the impact of patients’ genetic background on their sensitivity to carboplatin/paclitaxel hematotoxicity. Patients & methods: Parameters describing sensitivity to neutropenia and to thrombocytopenia of 201 patients were extracted from a previous pharmacokinetic/pharmacodynamics analysis, in order to assess their association with 52 candidates SNPs in 18 genes. Results: Carriers of a T allele of SLCO1B3-rs4149117 were 19% less sensitive to thrombocytopenia than the homozygotes for the G allele (p = 0.00279). Carriers of two copies of the ATG haplotypes of NR1I2-rs1523130, rs3814055 and rs1523127 were 19% less sensitive to thrombocytopenia than those harboring other haplotypes (p = 0.025). Conclusion: Our results revealed the importance of SLCO1B3 and NR1I2 in the sensitivity to carboplatin/paclitaxel thrombocytopenia.

Keywords::

• carboplatin
• drug metabolism
• hematotoxicity
• paclitaxel
• pregnane X receptor
• PXR
• SLCO1B3
• SNP

Financial & competing interests disclosure

This work was supported by a grant from Centre Hospitalier Universitaire (CHU) of Nîmes (France) and a grant from Cancéropôle Grand Sud-Ouest (France). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by a grant from Centre Hospitalier Universitaire (CHU) of Nîmes (France) and a grant from Cancéropôle Grand Sud-Ouest (France). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.