Title |
A Functional Variant at 19q13.3, rs967591G>A, Is Associated with Shorter Survival of Early-Stage Lung Cancer
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Published in |
Clinical Cancer Research, July 2013
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DOI | 10.1158/1078-0432.ccr-12-2792 |
Pubmed ID | |
Authors |
Hyo-Sung Jeon, 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 |
Abstract |
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. 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. 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). 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. |
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