Polymorphisms in SLCO1B3 and NR1I2 as genetic determinants of hematotoxicity of carboplatin and paclitaxel combination.
OBJECTIVE
The goal of our study was to assess the impact of patients' genetic background on their sensitivity to carboplatin/paclitaxel hematotoxicity.


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).


CONCLUSIONS
Our results revealed the importance of SLCO1B3 and NR1I2 in the sensitivity to carboplatin/paclitaxel thrombocytopenia.
Laboratoire de biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France.|IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, INSERM, U1194 France.|Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France.
Litaty Céphanoée
LC
Mbatchi
EA4553 Institut Claudius-Regaud, and Université Paul-Sabatier, Toulouse, France.
Antonin
A
Schmitt
EA4553 Institut Claudius-Regaud, and Université Paul-Sabatier, Toulouse, France.
Fabienne
F
Thomas
Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France.
Yoann
Y
Cazaubon
INSERM U916, Institut Bergonié, Université de Bordeaux, France.
Jacques
J
Robert
Laboratoire de biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France.
Serge
S
Lumbroso
Laboratoire de biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France.|IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, INSERM, U1194 France.
Jean-Paul
JP
Brouillet
IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, INSERM, U1194 France.
Philippe
P
Pourquier
EA4553 Institut Claudius-Regaud, and Université Paul-Sabatier, Toulouse, France.
Etienne
E
Chatelut
Laboratoire de biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France.
Jean-Christophe
JC
Boyer
Laboratoire de biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France.|IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, INSERM, U1194 France.|Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France.
Alexandre
A
Evrard
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; C000625852:NR1I2 protein, human; D029362:Organic Anion Transporters, Sodium-Independent; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D016190:Carboplatin; D017239:Paclitaxel
PXR; SLCO1B3; SNP; carboplatin; drug metabolism; hematotoxicity; paclitaxel; pregnane X receptor