title: Association of XRCC3 and XPD751 SNP with efficacy of platinum-based chemotherapy in advanced NSCLC patients.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, People's Republic of China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.forename: Vikramsingh
authors.initials: V
authors.lastname: Kim Curran
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Songwen
authors.initials: S
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D017671:Platinum Compounds; C110901:X-ray repair cross complementing protein 3; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human