MDM2 rs2279744 and TP53 rs1042522 polymorphisms associated with etoposide- and cisplatin-induced grade III/IV neutropenia in Chinese extensive-stage small-cell lung cancer patients

Oncol Res Treat. 2014;37(4):176-80. doi: 10.1159/000360785. Epub 2014 Mar 20.

Abstract

Background/aims: Etoposide and cisplatin (EP) chemotherapy is the most frequently used regimen in extensive-stage small-cell lung cancer (SCLC) patients, although the side effects (e.g., neutropenia) are high. This study investigates the association of the MDM2 rs2279744 and TP53 rs1042522 single-nucleotide polymorphisms (SNPs) with EP-induced grade III/IV neutropenia and with response to EP in extensive-stage SCLC patients.

Methods: Blood samples from 119 extensive-stage SCLC patients were subjected to genotyping of these 2 SNPs, using the allele-specific matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry for determining the association with neutropenia in the patients.

Results: The data showed that patients carrying the MDM2 rs2279744-GG genotype were associated with a lower incidence of grade III/IV neutropenia in the recessive and additive models, while the TP53 rs1042522-CC genotype was associated with a higher incidence in the recessive model. Furthermore, the combination of the MDM2 rs2279744-TT+TG and the TP53 rs1042522-CC genotype was associated with a significantly higher incidence of grade III/IV neutropenia. And the combination of the MDM2 rs2279744-GG and the TP53 rs1042522-GG+GC genotype was associated with the lowest incidence of grade III/IV neutropenia.

Conclusions: MDM2 rs2279744 and TP53 rs1042522 SNPs were associated with EP-induced high-grade neutropenia in extensive-stage SCLC patients. Further studies are needed to investigate the underlying mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • China / epidemiology
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neutropenia / chemically induced*
  • Neutropenia / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Retrospective Studies
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / pathology
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Etoposide
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Cisplatin