Oncotarget

Clinical Research Papers:

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 Jheon and Jae Yong Park

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Oncotarget. 2015; 6:24522-24532. https://doi.org/10.18632/oncotarget.4083

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Abstract

Shin Yup Lee1,2,*, Mi Jeong Hong3,10,*, Hyo-Sung Jeon3, Yi Young Choi3, Jin Eun Choi3,4, Hyo-Gyoung Kang3,4, Deuk Kju Jung3,10, Chengcheng Jin3,10, Sook Kyung Do3,10, Seung Soo Yoo1,2, Yangki Seok5, Eung Bae Lee5, Kyung Min Shin6, Ji Yun Jeong7, Won Kee Lee8, Jaehee Lee1, Seung Ick Cha1, Chang Ho Kim1, Young Tae Kim9, Sanghoon Jheon9, Jae Yong Park1,2,3,4,10

1Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

2Lung Cancer Center, Kyungpook National University Medical Center, Daegu, Republic of Korea

3Department of Biochemistry and Department of Cell Biology, and Kyungpook National University, Daegu, Republic of Korea

4Cell and Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea

5Thoracic Surgery, Kyungpook National University, Daegu, Republic of Korea

6Radiology, Kyungpook National University, Daegu, Republic of Korea

7Pathology, Kyungpook National University, Daegu, Republic of Korea

8Biostatistics Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

9Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Republic of Korea

10BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Jae Yong Park, e-mail: [email protected]

Keywords: ERCC1, polymorphisms, regulomeDB, lung cancer

Received: March 11, 2015     Accepted: May 13, 2015     Published: May 27, 2015

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.


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