Polymorphisms in SLCO1B3 and NR1I2 as genetic determinants of hematotoxicity of carboplatin and paclitaxel combination
Résumé
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.