ABCB1 and ABCC2 genetic polymorphism as risk factors for neutropenia in esophageal cancer patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy

Cancer Chemother Pharmacol. 2020 Aug;86(2):315-324. doi: 10.1007/s00280-020-04118-9. Epub 2020 Aug 3.

Abstract

Purpose: The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship between severe neutropenia and genetic polymorphisms in patients treated with preoperative DCF chemotherapy.

Methods: A total of 158 patients were investigated for their absolute neutrophil count (ANC) within the first cycle of DCF chemotherapy at the National Cancer Center (NCC) Hospital East. DNA samples obtained from the NCC Biobank Registry were used for the analysis of nine genetic polymorphisms related to docetaxel pharmacokinetics. These genotypes were evaluated for their association with severe neutropenia, and further their risk factors were examined using a multivariate logistic regression.

Results: A total 81 (51.3%) patients developed severe neutropenia. Multivariate analysis revealed that age (OR 1.054; CI 1.008-1.102, P = 0.022), baseline ANC (OR 1.019; CI 1.002-1.037, P = 0.030), ABCB1 3435C>T (OR 2.191; CI 1.087-4.417, P = 0.028) and ABCC2 *+9383C>G (OR 2.342; CI 1.108-4.948, P = 0.026) were significant risk factors for severe neutropenia development. The results from this study showed that age, ANC, ABCB1 3435C>T, and ABCC2 *+9383 G>C increased the incidence of severe neutropenia with the number of identified risk factors.

Conclusions: In addition to age and baseline ANC, ABCB1 3435C>T and ABCC2 *+9383C>G were identified as independent predictors for severe neutropenia in esophageal cancer patients treated with DCF chemotherapy.

Keywords: ABCB1 3435; ABCC2*; DCF chemotherapy; Esophageal cancer; Neutropenia; Polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Biomarkers, Tumor / genetics*
  • Cisplatin / administration & dosage
  • Docetaxel / administration & dosage
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics*
  • Neutropenia / chemically induced
  • Neutropenia / genetics
  • Neutropenia / pathology*
  • Polymorphism, Genetic*
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Biomarkers, Tumor
  • Multidrug Resistance-Associated Proteins
  • Docetaxel
  • multidrug resistance-associated protein 2
  • Cisplatin
  • Fluorouracil