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      • 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

        ( Shin Yup Lee ),( Jin Eun Choi ),( Hyo Sung Jeon ),( Mi Jung Hong ),( Yi Young Choi ),( Won Kee Lee ),( Seung Soo Yoo ),( Jae Hee Lee ),( Eung Bae Lee ),( Seung Ick Cha ),( Chang Ho Kim ),( Y Oung Ta 대한내과학회 2014 대한내과학회 추계학술발표논문집 Vol.2014 No.1

        Background: MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA-mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small cell lung cancer (NSCLC). Methods: Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom`s MassARRAY platform were investigated in 357 patients. A replication study was performed on an independent patient population (n = 479). Renilla luciferase assay and reverse transcription-PCR were conducted to examine functional relevance of potentially functional poly-miRTSs. Results: Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, KRT81 rs3660G>C was found to be associated with survival outcomes in the validation cohort. In combined analysis,patients with the rs3660 GC+CC genotype had a signifi cantly better overall survival (OS) compared with those with GG genotype (adjusted hazard ratio [aHR] for OS, 0.65; 95% confi dence interval [CI] 0.50-0.85; P= 0.001). An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expressionlevel of KRT81 in tumor tissues. Conclusions: The rs3660G>C affects KRT81 expression and thus infi uences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.

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