title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Yi-Zhuo
authors.initials: YZ
authors.lastname: Wang
authors.forename: Ke-Wei
authors.initials: KW
authors.lastname: Ma
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002681:China / Q000453:epidemiology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009503:Neutropenia / Q000139:chemically induced* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D002945:Cisplatin