A Functional Variant, rs967591G＞A, in the 19q13.3 and Survival of Early-Stage Lung Cancer

분야: 의약학 > 내과학
저자: 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 )
발행기관: 대한결핵 및 호흡기학회
간행물정보: 대한결핵및호흡기학회 추계학술발표초록집 2012년, 제114권 173(총1페이지)
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연관 논문

Poster Session : PS 1597 ; Lung Cancer : Association of Polymorphisms in the MicroRNA Target Sites and Survival of Patients in Early-Stage Non- Small-Cell Lung Cancer

Thematic Poster : TP-57 ; Association of Polymorphisms in the MicroRNA Target Sites and Survival of Patients in Early-Stage Non-Small-Cell Lung Cancer

Intronic variant of EGFR is associated with GBAS expression and survival outcome of early-stage non-small cell lung cancer

F-76 : Free Paper Presentation ; Replication of Results of a Genome-wide Association Study on Lung Cancer Survival in a Korean Population

Association between Common Genetic Polymorphisms in 1,994 Cancer-related Genes and Survival of Early-stage Non-small Cell Lung Cancer

영문초록

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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