Clinical outcome of cisplatin-based chemotherapy is associated with the polymorphisms of GSTP1 and XRCC1 in advanced non-small cell lung cancer patients

Clin Transl Oncol. 2015 Sep;17(9):720-6. doi: 10.1007/s12094-015-1299-6. Epub 2015 Jun 2.

Abstract

Introduction: This study is to evaluate the association of polymorphisms of glutathione S-transferase P1 (GSTP1), copper-transporting P-type adenosine triphosphatase A (ATP7A) and X-ray repair cross-complementing group 1 (XRCC1) with the efficacy and toxicity of cisplatin-based treatment in advanced non-small cell lung cancer (NSCLC) patients.

Materials and methods: The outcomes of 97 advanced non-small cell lung cancer patients treated with cisplatin-based chemotherapy were estimated. GSTP1, ATP7A, and XRCC1 genetic polymorphisms were determined via polymerase chain reaction of restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Association of the polymorphisms with the efficacy and toxicity of cisplatin was analyzed, respectively.

Results: Significant associations were observed between GSTP1 A313G and response rate (RR) (p = 0.027), disease control rate (DCR) (p = 0.019), and progression-free survival (PFS) (p = 0.044), respectively. Patients with AG and GG of GSTP1 have notably lower risk of anemia (p = 0.046). XRCC1 A1196G was associated with the incidence of lymphopenia (p = 0.024) and diarrhea (p = 0.020). ATP7A C2299G was not related with RR, DCR, PFS, and the risk of toxicity.

Conclusions: Advanced NSCLC patients with AA genotype of GSTP1 would obtain better curative effect followed with more risk of anemia when treated by cisplatin-based chemotherapy. ATP7A C2299G does not impact the efficacy and toxicity of cisplatin-based chemotherapy. XRCC1 1196A allele could predict the incidence of lymphopenia and diarrhea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenosine Triphosphatases / genetics
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cation Transport Proteins / genetics
  • Cisplatin / administration & dosage
  • Copper-Transporting ATPases
  • DNA-Binding Proteins / genetics*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Docetaxel
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Prognosis
  • Survival Rate
  • Taxoids / administration & dosage
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine
  • X-ray Repair Cross Complementing Protein 1

Substances

  • Biomarkers, Tumor
  • Cation Transport Proteins
  • DNA-Binding Proteins
  • Taxoids
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Deoxycytidine
  • Docetaxel
  • Vinblastine
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Adenosine Triphosphatases
  • ATP7A protein, human
  • Copper-Transporting ATPases
  • Paclitaxel
  • Cisplatin
  • Vinorelbine
  • Gemcitabine