Hyo-Sung Jeon 1 , Guang Jin , Hyo-Gyoung Kang , Yi Young Choi , Won Kee Lee , Jin Eun Choi , Eun Young Bae , Seung Soo Yoo , Shin Yup Lee , Eung Bae Lee , Young Tae Kim , Jaehee Lee , Seung-Ick Cha , Chang Ho Kim , Sanghoon Jheon , In San Kim , Jae Yong Park Show Affiliations »
Abstract
PURPOSE: 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. EXPERIMENTAL DESIGN: 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). CONCLUSION: 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. ©2013 AACR.
PURPOSE: 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. EXPERIMENTAL DESIGN: 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). CONCLUSION: 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. ©2013 AACR.
Entities: Disease
Gene
Mutation
Species
Mesh： See more »
Substances： See more »
Year: 2013
PMID： 23775331 DOI： 10.1158/1078-0432.CCR-12-2792
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531