TP53 Codon 72 Polymorphism Predicts Efficacy of Paclitaxel Plus Capecitabine Chemotherapy in Advanced Gastric Cancer Patients

Arch Med Res. 2016 Jan;47(1):13-8. doi: 10.1016/j.arcmed.2015.12.001. Epub 2015 Dec 13.

Abstract

Background and aims: The present study analyzed the relationship between TP53 codon 72 polymorphisms and the clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel chemotherapy.

Methods: Three hundred patients with advanced gastric cancer treated with paclitaxel and capecitabine combination chemotherapy were enrolled in the present study. Genomic DNA was extracted from peripheral blood leukocytes and determined using allele specific polymerase chain reaction (AS-PCR). Correlation between TP53 codon 72 polymorphisms and treatment response, gastric cancer survival was analyzed.

Results: The Pro/Pro genotypes of TP53 codon 72 were significantly correlated with a lower response rate to capecitabine plus paclitaxel chemotherapy in patients with gastric cancer when compared to the Arg/Arg genotype (30.6 vs. 63.2%, p value 0.000). Multivariate survival analysis also showed that the progression free survival (PFS) and overall survival (OS) for patients with Pro/Pro genotypes of TP53 codon 72 were worse than for those with the Arg/Arg genotype (hazard ratio [HR] = 2.177, p = 0.009; HR = 2.145, p = 0.038, respectively).

Conclusions: TP53 codon 72 polymorphisms was effective in predicting the response to chemotherapy and correlate with PFS and OS in patients with advanced gastric cancer treated with paclitaxel and capecitabine chemotherapy.

Keywords: Advanced gastric cancer; Capecitabine; Chemotherapy; Paclitaxel; TP53 polymorphism.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Capecitabine / administration & dosage
  • Capecitabine / pharmacology*
  • Capecitabine / therapeutic use
  • Codon / genetics*
  • Disease-Free Survival
  • Female
  • Genes, p53 / genetics*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use
  • Pharmacogenetics
  • Polymorphism, Genetic / genetics*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Treatment Outcome

Substances

  • Codon
  • Capecitabine
  • Paclitaxel