Clin Cancer Res 2013 Aug 17;19(15):4185-95. Epub 2013 Jun 17.
Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
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.