Association between polymorphisms of ERCC1 and XPD and clinical response to platinum-based chemotherapy in advanced non-small cell lung cancer

Am J Clin Oncol. 2010 Oct;33(5):489-94. doi: 10.1097/COC.0b013e3181b9cedc.

Abstract

Background and objective: DNA repair capacity is correlated with sensitivity of cancer cells toward platinum-based chemotherapy. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in polymorphisms of DNA repair gene ERCC1 (excision repair cross-complementation group 1) and XPD (ERCC2, excision repair cross-complementation group 2) were associated with the tumor response in advanced non-small-cell lung cancer (NSCLC) patients received platinum-based chemotherapy in Chinese population.

Methods: Totally 115 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin-based chemotherapy, and clinical response was evaluated after 2 cycles. Three dimensions (3-D) polyacrylamide gel-based DNA microarray method was used to evaluate the genotypes of ERCC1 Asn118Asn (354 CT), Gln504Lys (8092 CA) and XPD Lys751Gln (35931 AC).

Results: The C→T change of ERCC1 Asn118Asn polymorphism and the C→A change of ERCC1 Gln504Lys polymorphism have statistically significant association with elevated or descendent platinum-based chemotherapy response respectively.

Conclusion: The polymorphic status of ERCC1 might be the promising ancillary marker for predicting treatment response of advanced stage NSCLC patients. The DNA microarray-based method is accurate, high-throughput and inexpensive, suitable for SNP genotyping in a large number of individuals.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology
  • DNA-Binding Proteins / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Endonucleases / genetics*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide*
  • Treatment Outcome
  • Xeroderma Pigmentosum Group D Protein / genetics*

Substances

  • DNA-Binding Proteins
  • Carboplatin
  • ERCC1 protein, human
  • Endonucleases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Cisplatin