Functional intronic ERCC1 polymorphism from regulomeDB can predict survival in lung cancer after surgery

Shin Yup Lee, Mi Jeong Hong, Hyo Sung Jeon, Yi Young Choi, Jin Eun Choi, Hyo Gyoung Kang, Deuk Kju Jung, Chengcheng Jin, Sook Kyung Do, Seung Soo Yoo, Yangki Seok, Eung Bae Lee, Kyung Min Shin, Ji Yun Jeong, Won Kee Lee, Jaehee Lee, Seung Ick Cha, Chang Ho Kim, Young Tae Kim, Sanghoon JheonJae Yong Park

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 nonsmall 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.

Original languageEnglish
Pages (from-to)24522-24532
Number of pages11
JournalOncotarget
Volume6
Issue number27
DOIs
StatePublished - 2015

Keywords

  • ERCC1
  • Lung cancer
  • Polymorphisms
  • RegulomeDB

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