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Intronic variant of EGFR is associated with GBAS expression and survival outcome of early‐stage non‐small cell lung cancer

BACKGROUND: Genome‐wide association studies have indicated that most of the currently identified disease and trait‐associated single nucleotide polymorphisms (SNPs) are intronic or intergenic. RegulomeDB is a recently developed database that provides functional annotations for regulatory features of...

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Detalles Bibliográficos
Autores principales: Hong, Mi Jeong, Lee, Shin Yup, Choi, Jin Eun, Kang, Hyo‐Gyoung, Do, Sook Kyung, Lee, Jang Hyuck, Yoo, Seung Soo, Lee, Eung Bae, Seok, Yangki, Cho, Sukki, Jheon, Sanghoon, Lee, Jaehee, Cha, Seung Ick, Kim, Chang Ho, Park, Jae Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068432/
https://www.ncbi.nlm.nih.gov/pubmed/29806744
http://dx.doi.org/10.1111/1759-7714.12757
Descripción
Sumario:BACKGROUND: Genome‐wide association studies have indicated that most of the currently identified disease and trait‐associated single nucleotide polymorphisms (SNPs) are intronic or intergenic. RegulomeDB is a recently developed database that provides functional annotations for regulatory features of SNPs located in non‐coding regions. We evaluated the potential regulatory SNPs in the EGFR gene region using RegulomeDB and their associations with prognosis after surgery in non‐small cell lung cancer (NSCLC) patients. METHODS: A total of 698 patients with surgically resected NSCLC were enrolled and seven SNPs were selected based on the RegulomeDB database. All SNPs were genotyped using SEQUENOM MassARRAY iPLEX assay. RESULTS: Among the seven SNPs evaluated, rs9642391 (EGFR ivs19+2851C>G) was significantly associated with survival outcome (adjusted hazard ratio [HR] for overall survival = 0.70, 95% confidence interval [CI] 0.56–0.87, P = 0.001; adjusted HR for disease‐free survival = 0.82, 95% CI 0.70–0.97, P = 0.02; under a codominant model). According to RegulomeDB, rs9642391C>G, which is located in intron 19 of EGFR, was predicted to influence the expression of GBAS but not EGFR. As predicted, rs9642391C>G was associated with GBAS (P = 0.024) but not EGFR messenger RNA expression in tumor tissues. CONCLUSION: In conclusion, our study provides evidence that rs9642391C>G in the intron of EGFR is associated with GBAS expression and survival outcomes of patients with surgically resected early‐stage NSCLC.