title: Genome-wide association study on overall survival of advanced non-small cell lung cancer patients treated with carboplatin and paclitaxel.
abstract: OBJECTIVE
  Our goal was to identify candidate polymorphisms that could influence overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients treated with carboplatin (CBDCA) and paclitaxel (PTX).
  
  
  METHODS
  Chemotherapy-naïve stage IIIB or IV NSCLC patients treated with CBDCA (area under the curve = 6 mg/mL/min) and PTX (200 mg/m, 3-hour period) were eligible for this study. The DNA samples were extracted from peripheral blood mononuclear cells before treatment, and genotypes at approximately 110,000 gene-centric single-nucleotide polymorphisms (SNPs) were obtained by Illumina's Sentrix Human-1 Genotyping BeadChip. Statistical analyses were performed by the log-rank test and Cox proportional hazards model.
  
  
  RESULTS
  From July 2002 to May 2004, 105 patients received a total of 308 cycles of treatment. The median survival time (MST) of 105 patients was 17.1 months. In the genome-wide association study, three SNPs were associated significantly with shortened OS after multiple comparison adjustment: rs1656402 in the EIF4E2 gene (MST was 18.0 and 7.7 months for AG [n = 50] + AA [n = 40] and GG [n = 15], respectively; p = 8.4 × 10), rs1209950 in the ETS2 gene (MST = 17.7 and 7.4 months for CC [n = 94] and CT [n = 11] + TT [n = 0]; p = 2.8 × 10), and rs9981861 in the DSCAM gene (MST = 17.1 and 3.8 months for AA [n = 75] + AG [n = 26] and GG [n = 4]; p = 3.5 × 10).
  
  
  CONCLUSIONS
  Three SNPs were identified as new prognostic biomarker candidates for advanced NSCLC treated with CBDCA and PTX. The agnostic genome-wide association study may unveil unexplored molecular pathways associated with the drug response, but our findings should be replicated by other investigators.
authors.affiliation: Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.forename: Nan M
authors.initials: NM
authors.lastname: Laird
authors.forename: Noriko
authors.initials: N
authors.lastname: Katori
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Sumiko
authors.initials: S
authors.lastname: Ohnami
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sawada
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D004273:DNA, Neoplasm; D016190:Carboplatin; D017239:Paclitaxel