title: Genome-wide examination of genetic variants associated with response to platinum-based chemotherapy in patients with small-cell lung cancer.
abstract: OBJECTIVE
  Small-cell lung cancer (SCLC) accounts for about 20% of total lung cancer, and systemic chemotherapy is the major therapy for all stages of SCLC. Although most SCLC patients are characterized by initial chemosensitivity to the standard first-line platinum-based regimens, a significant fraction of patients are intrinsic nonresponders.
  
  
  METHODS
  Genome-wide scan of 440 093 single-nucleotide polymorphisms (SNPs) was conducted using peripheral blood DNA to identify variants associated with response to first-line carboplatin or cisplatin plus etoposide chemotherapy in 245 patients with SCLC and the results were replicated in another set of 183 patients.
  
  
  RESULTS
  By set association analysis, 20 SNPs were identified to be associated with treatment response, with odds ratios (95% confidence interval) ranging from 2.36 (1.56-3.57) to 4.38 (2.12-9.29) and these results were confirmed in the replication phase. Most of these SNPs (14/20) were clustered on chromosomes 22p11.23, 6q24.3, and 20p12.2 containing BTBD3, STXBP5, and BCR genes.
  
  
  CONCLUSIONS
  Germline genetic variations influence the effectiveness of platinum-based chemotherapy of SCLC and further studies are needed to test the value of these findings for personalized chemotherapy.
authors.affiliation: The State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Binghe
authors.initials: B
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Yin
authors.initials: Y
authors.lastname: Guan
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shen
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005796:Genes; D016678:Genome; D006801:Humans; D004930:Inuit / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010984:Platinum / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D050683:R-SNARE Proteins; D055752:Small Cell Lung Carcinoma
chemical_list: D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; C484767:STXBP5 protein, human; D010984:Platinum; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin