1. Functional intronic ERCC1 polymorphism from regulomeDB can predict survival in lung cancer after surgery.
- Author
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Lee SY, Hong MJ, Jeon HS, Choi YY, Choi JE, Kang HG, Jung DK, Jin C, Do SK, Yoo SS, Seok Y, Lee EB, Shin KM, Jeong JY, Lee WK, Lee J, Cha SI, Kim CH, Kim YT, Jheon S, and Park JY
- Subjects
- Asian People, Carcinoma, Non-Small-Cell Lung surgery, Databases, Genetic, Disease-Free Survival, Female, Genetic Association Studies, Humans, Kaplan-Meier Estimate, Lung Neoplasms surgery, Male, Middle Aged, Polymorphism, Single Nucleotide genetics, Promoter Regions, Genetic genetics, Republic of Korea, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung mortality, DNA-Binding Proteins genetics, Endonucleases genetics, Lung Neoplasms genetics, Lung Neoplasms mortality
- Abstract
We searched for potential regulatory single nucleotide polymorphisms (SNPs) in excision repair cross-complementing group 1 (ERCC1) using RegulomeDB, a database integrating information from the Encyclopedia of DNA Elements (ENCODE) project, and investigated their association with survival after surgery in non-small cell lung cancer (NSCLC). Among 364 SNPs found within ERCC1 region using RegulomeDB, four top priority SNPs (rs2298881C>A, rs1049739A>G, rs10415949A>G and rs6509214G>T) were selected for this study. The four SNPs were investigated in 316 patients. A replication study was performed (n = 579). Of the four SNPs analyzed in the discovery set, rs2298881C>A and rs6509214G>T were significantly associated with survival outcomes. The association was consistently observed only for rs2298881C>A in the validation cohort. In combined analysis, rs2298881C>A was significantly associated with worse overall survival and disease-free survival (P = 0.0002 and 0.02, respectively). A decreased reporter gene expression for rs2298881 A allele was observed compared with C allele by luciferase assay (P = 0.02). ERCC1 rs2298881C>A, an intronic SNP, is the first genetic polymorphism with functional evidence of regulating its expression, and the SNP is associated with prognosis of NSCLC. Our result supports the role of RegulomeDB as a comprehensive source of prioritized candidate SNPs for genetic association studies.
- Published
- 2015
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