title: Functional intronic ERCC1 polymorphism from regulomeDB can predict survival in lung cancer after surgery.
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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors.forename: Shin Yup
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Hong
authors.affiliation: Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.affiliation: Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Yi Young
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Hyo-Gyoung
authors.initials: HG
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Deuk Kju
authors.initials: DK
authors.lastname: Jung
authors.affiliation: Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Sook Kyung
authors.initials: SK
authors.lastname: Do
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.affiliation: Thoracic Surgery, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Yangki
authors.initials: Y
authors.lastname: Seok
authors.affiliation: Thoracic Surgery, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Eung Bae
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Radiology, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Shin
authors.affiliation: Pathology, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Biostatistics Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jaehee
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Seung Ick
authors.initials: SI
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Jheon
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.|Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea.|Department of Biochemistry and Department of Cell Biology, Kyungpook National University, Daegu, Republic of Korea.|Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea.|BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D004268:DNA-Binding Proteins / Q000235:genetics*; D030541:Databases, Genetic; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D056910:Republic of Korea
chemical_list: D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: ERCC1; lung cancer; polymorphisms; regulomeDB