A Functional Variant, rs967591G>A, in the 19q13.3 and Survival of Early-Stage Lung Cancer
의약학 > 내과학
박재용 , ( Hyo Sung Jeon ) , ( Seung Soo Yoo ) , ( Shin Yup Lee ) , ( Jaehee Lee ) , ( Seung Ick Cha ) , ( Chang Ho Kim ) , ( Eung Bae Lee ) , ( Young Tae Kim ) , ( Sang Hoon Jheon )
대한결핵 및 호흡기학회
대한결핵및호흡기학회 추계학술발표초록집 2012년, 제114권 173(총1페이지)
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    Purpose: This study was conducted to investigate the associations between single nucleotide polymorphisms (SNPs) in 19q13.3 and survival of early-stage non-small cell lung cancer (NSCLC) patients, 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=565). Luciferase assay and real-time PCR was performed 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 1 study. The rs967591A allele had significantly higher promoter activity of CD3EAP compared with the rs967591G allele (P=0.002), but the SNP did not have an effect on the promoter activity of PPP1R13L. 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 2 study. In combined analysis, the rs967591 AA genotype exhibited a worse overall survival (adjusted hazard ratio=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.
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