-216G/T (rs712829), a functional variant of the EGFR promoter, is associated with the pleural metastasis of lung adenocarcinoma

Guo,Haisheng; Xing,Yunhui; Liu,Ruibao; Chen,Shaoping; Bian,Xia; Wang,Fang; Yang,Chunmei; Wang,Xunguo

doi:10.3892/ol.2013.1442

-216G/T (rs712829), a functional variant of the EGFR promoter, is associated with the pleural metastasis of lung adenocarcinoma

Authors:
- Haisheng Guo
- Yunhui Xing
- Ruibao Liu
- Shaoping Chen
- Xia Bian
- Fang Wang
- Chunmei Yang
- Xunguo Wang
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Affiliations: Department of Oncology, Dongying People's Hospital, Dongying, Shandong 257091, P.R. China, Department of Tuberculosis, Shengli Hospital of Shengli Oilfield, Dongying, Shandong 257075, P.R. China
Published online on: July 3, 2013 https://doi.org/10.3892/ol.2013.1442
Pages: 693-698

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Abstract

Numerous mutations and variants in the epidermal growth factor receptor (EGFR) gene have been demonstrated to be associated with the occurrence, metastasis and prognosis of various types of tumors, including lung cancer. Thus, the present study aimed to investigate whether ‑216G/T (rs712829), a functional polymorphism of the EGFR promoter that is able to induce EGFR activation and overexpression, is associated with the pleural metastasis of lung adenocarcinoma. The study subjects were comprised of 326 patients with primary lung adenocarcinoma and 312 matched cases with pleural metastasis. The ‑216G/T genotypes were determined in all subjects by PCR amplification and direct DNA sequencing, and EGFR expression was also evaluated by immunohistochemical staining in the primary tumor tissues with various ‑216G/T genotype backgrounds. The results showed that the frequencies of allele T and genotypes G/T and T/T in the pleural metastasis group were significantly higher compared with those in the non‑metastasis group, with adjusted ORs of 1.46 (95% CI, 1.015‑1.963) for G/T and 1.97 (95% CI, 1.051‑3.152) for T/T. Furthermore, the expression of the EGFR protein was higher in the primary lung adenocarcinoma tissues with ‑216T/T and ‑216G/T compared with those with ‑216G/G (P<0.05). These results collectively indicate that the ‑216G/T polymorphism in the EGFR promoter is associated with the risk of the pleural metastasis of lung adenocarcinoma and that this effect may be associated with ‑216G/T‑induced overexpression of the EGFR protein.

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