Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum-based chemotherapy in advanced nonsmall-cell lung cancer patients

Int J Cancer. 2014 Dec 1;135(11):2687-96. doi: 10.1002/ijc.28892. Epub 2014 Apr 25.

Abstract

Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum-based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1-141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall-cell lung cancer (NSCLC) patients after treatment with platinum-based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p = 0.005], while XRCC1 399 GA, or GA+AA, was associated with poor OS in short-term period (HR 1.718, p = 0.003; HR 1.691, p = 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short-term period (HR 1.929, p < 0.001). Furthermore, patients with XRCC1 399 variant allele (GA+AA) had higher risk of hematologic toxicity (p = 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1-141 GG variant, had reduced risk of gastrointestinal toxicity (p = 0.015 and p = 0.023, respectively). The data from the current study provide evidence that OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1-141T/G polymorphisms may be useful in predicting clinical outcomes in patients with advanced inoperable NSCLC that will undergo platinum-based chemotherapy.

Keywords: base excision repair; chemotherapy; nonsmall-cell lung cancer; polymorphisms; toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • 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 / secondary
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Case-Control Studies
  • Cisplatin / administration & dosage
  • DNA Glycosylases / genetics*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics*
  • DNA-Binding Proteins / genetics*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Docetaxel
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Prospective Studies
  • Survival Rate
  • Taxoids / administration & dosage
  • X-ray Repair Cross Complementing Protein 1

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Taxoids
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Deoxycytidine
  • Docetaxel
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Paclitaxel
  • Cisplatin
  • Gemcitabine