Association of XRCC3 and XPD751 SNP with efficacy of platinum-based chemotherapy in advanced NSCLC patients

Clin Transl Oncol. 2012 Mar;14(3):207-13. doi: 10.1007/s12094-012-0785-3.

Abstract

Introduction: The aim of this study was to investigate whe- ther X-ray repair cross-complementing group 3 (XRCC3) and xeroderma pigmentosum group D (XPD) single nucleotide polymorphism (SNP) affects the outcome of platinum- based chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients.

Material and methods: From September 2005 to June 2009, 355 advanced-stage NSCLC patients were accrued to compare the SNP variants with the outcome of platinum-based chemotherapy. TaqMan RT-PCR was used to evaluate the SNPs of the XRCC3 codon241 (Thr/Met) and XPD codon751 (Lys/Gln) DNA repair genes.

Results: There was a lack of association between the studied SNPs and the response rate, progression-free survival or overall survival (OS) in the whole population. However, subgroup analysis revealed that XRCC3 241 Thr/Met or Met/Met allele was associated with marginally significantly longer OS than XRCC3 Thr/Thr allele (19.0 m vs. 12.5 m, p=0.081) in the patients treated with gemcitabine/ cisplatin or carboplatin (GP/GC) while it was correlated with a significantly shorter OS in the patients treated with non GP/GC (9.3 m vs. 16 m, p=0.003). XPD751 Lys/Lys had an association with statistical significantly longer OS than XPD751 Lys/Gln or Gln/Gln in the subgroup of elderly patients (14.10 m vs. 10 m, p=0.019) and patients with non-adenocarcinoma (12.6 m vs. 9 m, p=0.042).

Conclusions: XRCC3 Thr241Met played an opposite role in predicting prognosis of chemotherapy in NSCLC patients according to the first-line regimens. XPD 751 Lys/ Lys might be a better prognostic marker of elderly or noncarcinoma NSCLC subgroup treated with platinum-based chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Pharmacological / metabolism
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Clinical Trials as Topic
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Genetic Association Studies
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Platinum Compounds / administration & dosage
  • Polymorphism, Single Nucleotide / physiology
  • Prognosis
  • Survival Analysis
  • Treatment Outcome
  • Xeroderma Pigmentosum Group D Protein / genetics*

Substances

  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Platinum Compounds
  • X-ray repair cross complementing protein 3
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human