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

Litaty Céphanoée Mbatchi; Antonin Schmitt; Fabienne Thomas; Yoann Cazaubon; Jacques Robert; Serge Lumbroso; Jean-Paul Brouillet; Philippe Pourquier; Etienne Chatelut; Jean-Christophe Boyer; Alexandre Evrard

doi:10.2217/pgs.15.84

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

Pharmacogenomics. 2015;16(13):1439-50. doi: 10.2217/pgs.15.84. Epub 2015 Aug 12.

Authors

Litaty Céphanoée Mbatchi^{1

2

3}, Antonin Schmitt⁴, Fabienne Thomas⁴, Yoann Cazaubon³, Jacques Robert⁵, Serge Lumbroso¹, Jean-Paul Brouillet^{1

2}, Philippe Pourquier², Etienne Chatelut⁴, Jean-Christophe Boyer¹, Alexandre Evrard^{1

2

3}

Affiliations

¹ Laboratoire de biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France.
² IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, INSERM, U1194 France.
³ Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France.
⁴ EA4553 Institut Claudius-Regaud, and Université Paul-Sabatier, Toulouse, France.
⁵ INSERM U916, Institut Bergonié, Université de Bordeaux, France.

PMID: 26267044
DOI: 10.2217/pgs.15.84

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: PXR; SLCO1B3; SNP; carboplatin; drug metabolism; hematotoxicity; paclitaxel; pregnane X receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Alleles
Antineoplastic Agents / administration & dosage
Antineoplastic Agents, Phytogenic / administration & dosage
Carboplatin / administration & dosage
Cohort Studies
Female
Gene Frequency
Genetic Association Studies
Haplotypes
Humans
Linkage Disequilibrium
Male
Middle Aged
Organic Anion Transporters, Sodium-Independent / genetics*
Paclitaxel / administration & dosage
Polymorphism, Single Nucleotide
Pregnane X Receptor
Receptors, Steroid / genetics*
Solute Carrier Organic Anion Transporter Family Member 1B3
Thrombocytopenia / chemically induced*
Thrombocytopenia / epidemiology
Thrombocytopenia / genetics*
Young Adult

Substances

Antineoplastic Agents
Antineoplastic Agents, Phytogenic
NR1I2 protein, human
Organic Anion Transporters, Sodium-Independent
Pregnane X Receptor
Receptors, Steroid
SLCO1B3 protein, human
Solute Carrier Organic Anion Transporter Family Member 1B3
Carboplatin
Paclitaxel