title: -216G/T (rs712829), a functional variant of theEGFRpromoter, is associated with the pleural metastasis of lung adenocarcinoma.
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 theEGFRpromoter that is able to induceEGFRactivation 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, andEGFRexpression 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.
authors.affiliation: Department of Oncology, Dongying People's Hospital, Dongying, Shandong 257091, P.R. China.
authors.forename: Haisheng
authors.initials: H
authors.lastname: Guo
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Xing
authors.forename: Ruibao
authors.initials: R
authors.lastname: Liu
authors.forename: Shaoping
authors.initials: S
authors.lastname: Chen
authors.forename: Xia
authors.initials: X
authors.lastname: Bian
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Chunmei
authors.initials: C
authors.lastname: Yang
authors.forename: Xunguo
authors.initials: X
authors.lastname: Wang
keywords: EGFR; gene polymorphism; lung adenocarcinoma; pleural metastasis