title: Polymorphism of CYP3A4 and ABCB1 genes increase the risk of neuropathy in breast cancer patients treated with paclitaxel and docetaxel.
abstract: BACKGROUND
  Interindividual variability of pharmacogenetics may account for unpredictable neurotoxicities of taxanes.
  
  
  METHODS
  From March 2011 to June 2015, female patients with operable breast cancer who had received docetaxel- or paclitaxel-containing adjuvant chemotherapy were included in this study. All patients were treated with single-agent paclitaxel intravenously (IV) 175 mg/m(2) every 3 weeks for four cycles, or IV 80 mg/m(2) weekly for 12 cycles, and IV 100 mg/m(2) docetaxel for four cycles as adjuvant treatment. We evaluated the relationship between neurotoxicity of taxanes and single-nucleotide polymorphisms of ABCB1, CYP3A4, ERCC1, ERCC2, FGFR4, TP53, ERBB2, and CYP2C8 genes. Taxane-induced neurotoxicity during the treatment was evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.03 prior to each cycle. Chi-squared tests were used to compare the two groups, and multivariate binary logistic regression models were used for determining possible risk factors of neuropathy.
  
  
  RESULTS
  Pharmacogenetic analysis was performed in 219 females. ABCB1 3435 TT genotype had significantly higher risk for grade ≥2 neurotoxicity (odds ratio [OR]: 2.759, 95% confidence interval [CI]: 1.172-6.493, P: 0.017) compared to TC and CC genotype, and also CYP3A4 392 AA and AG genotype had significantly higher risk for grade ≥2 neurotoxicity (OR: 2.259, 95% CI: 1.033-4.941, P: 0.038) compared to GG genotype. For FDGF4 gene with AG and GG genotype, OR was 1.879 (95% CI: 1.001-3.525, P: 0.048) compared to AA genotype with regard to any grade of neuropathy risk. We could not find any other association of other genotypes with neurotoxicity grades.
  
  
  CONCLUSIONS
  ABCB1 3435 TT genotype and CYP3A4 392 AA/AG genotypes may be used as predictors of neurotoxicity during taxane chemotherapy.
authors: Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Gaziantep Oncology Hospital, Gaziantep, Turkey.
authors: Tulay
authors: T
authors: Kus
authors: Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Gaziantep Oncology Hospital, Gaziantep, Turkey.
authors: Gokmen
authors: G
authors: Aktas
authors: Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Gaziantep Oncology Hospital, Gaziantep, Turkey.
authors: Mehmet Emin
authors: ME
authors: Kalender
authors: Department of Medical Pharmacology.
authors: Abdullah Tuncay
authors: AT
authors: Demiryurek
authors: Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Gaziantep Oncology Hospital, Gaziantep, Turkey.
authors: Mustafa
authors: M
authors: Ulasli
authors: Department of Medical Biology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.
authors: Serdar
authors: S
authors: Oztuzcu
authors: Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Gaziantep Oncology Hospital, Gaziantep, Turkey.
authors: Alper
authors: A
authors: Sevinc
authors: Department of Biostatistics, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.
authors: Seval
authors: S
authors: Kul
authors: Department of Internal Medicine, Division of Medical Oncology, University of Gaziantep, Gaziantep Oncology Hospital, Gaziantep, Turkey.
authors: Celaletdin
authors: C
authors: Camci
keywords: ABCB1; CYP3A4; docetaxel; neurotoxicity; paclitaxel; single nucleotide polymorphisms