-216G/T (rs712829), a functional variant of the EGFR promoter, 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 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.

Progression and metastasis of lung cancer

“…Interestingly, when comparing adenocarcinomas with known driver mutation, it is evident that adenocarcinomas with EML4-ALK1 rearrangement have a higher propensity for pleura metastasis and malignant effusion [ 124 ]. In one study, it was proposed that the 216G/T polymorphism of the EGF receptor may play a role in pleural metastasis by overexpressing the protein [ 125 ].…”

Association of Genetic Polymorphisms of EGFR with Glioma in a Chinese Population

“…The epidermal growth factor receptor (EGFR) is involved in human tumors by regulating important cellular processes (Guo et al, 2013). Previous studies have reported singlenucleotide polymorphisms (SNPs) in the EGFR gene to be associated with several kinds of cancers, including lung cancer (He et al, 2013), breast cancer (Connor et al, 2013), and esophageal cancer (Lee et al, 2011).…”

The Association between Epidermal Growth Factor Receptor (EGFR) Gene Polymorphisms and Lung Cancer Risk

“…Moreover, a significant association was also found between rs712829 and the risk of lung cancer of the adenocarcinoma subtype. A previous study reported an association between the rs712829 TT genotype and the pleural metastasis of lung adenocarcinoma in the Chinese population [26]. In addition, a lack of association between the rs712829 SNP and lung cancer was reported in a United States population [18] and a Japanese population [19].…”