Association between Common Genetic Polymorphisms in 1,994 Cancer-related Genes and Survival of Early-stage Non-small Cell Lung Cancer
의약학 > 내과학
유승수 , ( Yi Young Cho ) , ( Hyo Sung Jeon ) , ( Shin Yup Lee ) , ( Yang Ki Seok ) , ( Jae Hee Lee ) , ( Seung Ick Cha ) , ( Chang Ho Kim ) , ( Eung Bae Lee ) , ( Young Tae Kim ) , ( Sang Hoon Jheon ) , ( Jae Yong Park )
대한결핵 및 호흡기학회
대한결핵및호흡기학회 추계학술발표초록집 2012년, 제114권 173(총1페이지)
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    Purpose: This study was conducted to identify genetic polymorphisms associated with the prognosis of patients with early-stage non-small cell lung cancer (NSCLC). Materials and Methods: We genotyped 2,228 potentially functional single nucleotide polymorphisms (SNPs) of 1,994 genes using the Affymetrix custom-made GeneChip, which were related to the development and progression of cancer, in 166 NSCLC patients who underwent curative surgical resection. A replication study was performed on an independent cohort of 626 patients. The functional effect of GNB2L1 SNPs was evaluated by promoter assay and electrophoretic mobility shift assay (EMSA). Results: Among 2,228 SNPs, 13 SNPs which were associated with overall survival (OS) and/or disease-free survival (DFS) with log-rank P values lower than 0.10 in a discovery set were selected for validation. Among the 13 validation SNPs, 5 SNPs (C3 rs2287845, GNB2L1 rs1279736 and rs3756585, FANCD2 rs7647987, and SCGB1D2 rs2232950) were found to be associated with survival outcomes in the same direction as the discovery set. In combined analysis, the rs1279736 and rs3756585 were most significantly associated with OS and DFS in multivariate analysis (p for OS<0.0001, both; and P for DFS=0.003, both; under a codominant model). The promoter assay and EMSA revealed that the rs3795685 lead to change of promoter activity and binding of transcription factors. Conclusions: We identified five SNPs as markers for prognosis of patients with surgically resected NSCLC.
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