title: Polymorphisms of ERCC1 C118T/C8092A and MDR1 C3435T predict outcome of platinum-based chemotherapies in advanced non-small cell lung cancer: a meta-analysis.
abstract: OBJECTIVE
  With great progress made in individualized chemotherapy, pharmacogenetics is gradually put on the agenda. We performed this meta-analysis to compare outcome to platinum-based chemotherapies in advanced non-small cell lung cancer (NSCLC) with different ERCC1 C118T/C8092A and MDR1 C3435T polymorphisms.
  
  
  METHODS
  Relevant studies were identified according to search strategy in this meta-analysis. Inclusion criteria were patients with advanced NSCLC who were receiving platinum-based chemotherapies. We evaluated the relationship between single nucleotide polymorphisms (SNP) and outcome of platinum-based chemotherapies. RevMan and STATA package were used for the comprehensive quantitative analyses.
  
  
  RESULTS
  Twenty studies were included in the meta-analysis. There was no significant association between SNPs and objective response or overall survival of platinum-based chemotherapies with CC vs. CT/TT: ERCC1 C118T (OR 1.21, 95% CI 0.81-1.82 for objective response; HR 1.09, 95% CI 0.79-1.51 for overall survival); ERCC1 C8092A SNP (OR 0.84, 95% CI 0.59-1.18; HR 1.26, 95% CI 0.68-2.36) and MDR1 C3435T SNP (HR 1.11, 95% CI 0.78-1.56). Ethnic stratification provided the same results. We found a significant difference for MDR1 C3435T (OR 2.22, 95% CI 1.46-3.37; OR 2.63, 95% CI 1.56-4.45 for Asians; OR 1.61, 95% CI 0.79-3.28 for Caucasians).
  
  
  CONCLUSIONS
  We found no evidence to support the use of ERCC1 C118T/C8092A polymorphisms as prognostic predictors of platinum-based chemotherapies in NSCLC. For the MDR1 C3435T SNP, a significant association with objective response was detected for CC genotype in overall and Asian populations stratified. Multiple and large-scale studies with ethnic stratification are required for the correlation between biomarkers and tumor prognosis.
authors.affiliation: Department of Oncology Medicine, The 3(rd) Affiliated Hospital, Harbin Medical University, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Wei
authors.forename: Xiang-Shi
authors.initials: XS
authors.lastname: Lu
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Shang
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: De-Hai
authors.initials: DH
authors.lastname: Che
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Guang-Mei
authors.initials: GM
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases