A Functional Variant at 19q13.3, rs967591G %26gt; A, Is Associated with Shorter Survival of Early-Stage Lung Cancer

作者：Jeon Hyo Sung; Jin Guang; Kang Hyo Gyoung; Choi Yi Young; Lee Won Kee; Choi Jin Eun; Bae Eun Young; Yoo Seung Soo; Lee Shin Yup; Lee Eung Bae; Kim Young Tae; Lee Jaehee; Cha Seung Ick; Kim Chang Ho; Jheon Sanghoon; Kim In San; Park Jae Yong^*

来源：Clinical Cancer Research, 2013, 19(15): 4185-4195.

DOI：10.1158/1078-0432.CCR-12-2792

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. %26lt;br%26gt;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. %26lt;br%26gt;Results: Of the five SNPs, three SNPs (rs105165C%26gt;T, rs967591G%26gt;A, and rs735482A%26gt;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%26gt;A was associated with the level of CD3EAP mRNA expression in lung tissues (P = 0.01). The rs967591G%26gt;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). %26lt;br%26gt;Conclusion: The rs967591G%26gt;A affects CD3EAP expression and thus influences survival in early-stage NSCLC. The analysis of the rs967591G%26gt;A polymorphism can help identify patients at high risk of a poor disease outcome.

• 出版日期2013-8-1
• 单位延边大学