title: A functional variant at 19q13.3, rs967591G>A, is associated with shorter survival of early-stage lung cancer.
abstract: OBJECTIVE
  This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) in 19q13.3 and survival of patients with early-stage non-small cell lung cancer (NSCLC), and to define the causative functional SNP of the association.
  
  
  METHODS
  A two-stage study design was used to evaluate five SNPs in relation to survival outcomes in 328 patients and then to validate the results in an independent patient population (n = 483). Luciferase assay and real-time PCR were conducted to examine functional relevance of a potentially functional SNP.
  
  
  RESULTS
  Of the five SNPs, three SNPs (rs105165C>T, rs967591G>A, and rs735482A>C) were significantly associated with survival outcomes in a stage I study. The rs967591A allele had significantly higher activity of the CD3EAP promoter compared with the rs967591G allele (P = 0.002), but the SNP did not have an effect on the activity of PPP1R13L promoter. The rs967591G>A was associated with the level of CD3EAP mRNA expression in lung tissues (P = 0.01). The rs967591G>A exhibited consistent associations in a stage II study. In combined analysis, the rs967591 AA genotype exhibited a worse overall survival (adjusted HR = 1.69; 95% confidence interval = 1.29-2.20; P = 0.0001).
  
  
  CONCLUSIONS
  The rs967591G>A affects CD3EAP expression and thus influences survival in early-stage NSCLC. The analysis of the rs967591G>A polymorphism can help identify patients at high risk of a poor disease outcome.
authors.affiliation: Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Hyo-Gyoung
authors.initials: HG
authors.lastname: Kang
authors.forename: Yi Young
authors.initials: YY
authors.lastname: Choi
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Bae
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.forename: Shin Yup
authors.initials: SY
authors.lastname: Lee
authors.forename: Eung Bae
authors.initials: EB
authors.lastname: Lee
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.forename: Jaehee
authors.initials: J
authors.lastname: Lee
authors.forename: Seung-Ick
authors.initials: SI
authors.lastname: Cha
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Jheon
authors.forename: In San
authors.initials: IS
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D016019:Survival Analysis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; C119975:POLR1G protein, human; D012318:RNA Polymerase I