title: Polymorphisms in XPD gene could predict clinical outcome of platinum-based chemotherapy for non-small cell lung cancer patients: a meta-analysis of 24 studies.
abstract: OBJECTIVE
  Xeroderma pigmentosum group D (XPD) is an essential gene involved in the nucleotide excision repair (NER) pathway. Two commonly studied single nucleotide polymorphisms (SNPs) of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793) are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  A comprehensive search of PubMed database was conducted to identify relevant articles. Primary outcomes included objective response (i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS) and overall survival (OS). The pooled and 95% confidence intervals (CIs) of ORs (odds ratios) and HRs (hazard ratios) were estimated using the fixed or random effect model.
  
  
  RESULTS
  Twenty-four studies were eligible according to the inclusion criteria. None of the XPD Lys751Gln/Asp312Asn polymorphisms was associated with objective response, PFS or OS in NSCLC patients treated with platinum drugs. However, in stratified analysis by ethnicity, the XPD Lys751Gln (A>C) polymorphism was not significantly associated with increased response in Caucasians (OR=1.35, 95%CI=1.0-1.83, P=0.122 for heterogeneity) but was associated with decreased PFS in Asians (HR=1.39, 95%CI=1.07-1.81, P=0.879 for heterogeneity). Furthermore, a statistically significant difference existed in the estimates of effect between the two ethnicities (P=0.014 for TR; P<0.001 for PFS).
  
  
  CONCLUSIONS
  XPD Lys751Gln (A>C) may have inverse predictive and prognostic role in platinum-based treatment of NSCLC according to different ethnicities. Further studies are needed to validate our findings.
authors.affiliation: Department of Radiation Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Zhu
authors.forename: Baixia
authors.initials: B
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.forename: Hongyan
authors.initials: H
authors.lastname: Cheng
authors.forename: Jianxin
authors.initials: J
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhan
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Zheming
authors.initials: Z
authors.lastname: Liu
authors.forename: Liping
authors.initials: L
authors.lastname: Xu
authors.forename: Xinchen
authors.initials: X
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human