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Thorac Cancer. 2018 Aug;9(8):916-923. doi: 10.1111/1759-7714.12757. Epub 2018 May 28.

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

Hong MJ1, Lee SY2,3, Choi JE1, Kang HG1, Do SK4,5, Lee JH4,5, Yoo SS2,3, Lee EB3,6, Seok Y3,6, Cho S7, Jheon S7, Lee J2, Cha SI2, Kim CH2, Park JY1,2,3,4,5.

Author information

1
Department of Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
2
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.
3
Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Korea.
4
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.
5
BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Korea.
6
Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea.
7
Department of Thoracic and Cardiovascular Surgery, Seoul National University School of Medicine, Seoul, Korea.

Abstract

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.

KEYWORDS:

EGFR; RegulomeDB; lung cancer; survival

PMID:
29806744
PMCID:
PMC6068432
DOI:
10.1111/1759-7714.12757
[Indexed for MEDLINE]
Free PMC Article

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