Impact of the -216G/T Polymorphism on the Sp1 and Epidermal Growth Factor Receptor Interaction in Non-Small Cell Lung Carcinoma

Abstract

The epidermal growth factor receptor is central to the growth, differentiation and the mobility of normal and cancer cells. Notably, EGFR plays an important role in non-small cell lung carcinoma development. Two known nucleotide variants in EGFR promoter at position -216 (G > T) and -191 (C > A) are known to influence promoter activity. The transcription factor Sp1 (Specificity protein 1) binds with higher affinity the T allele at position -216 which results in 30% increased transcriptional activity of EGFR. Sequencing of EGFR promoter region and exon 1 in 18 patients with pulmonary carcinoma revealed that -216 G/T variant was associated with 58.82% of NSCLC patients especially those with squamous carcinoma, with predominance of homozygote (T/T) variants. Strikingly, the -191C/A polymorphism was detected in 11.11% of patients having a pulmonary carcinoma with the predominance of homozygote (C/C) variants. The distribution analysis of the four haplotypes (G-C, G-A, T-C and T-A) and the diplotype (G-C/T-C) of -216G/T and -191C/A polymorphisms, revealed a clear predominance of T-C haplotype (216T-191C) in squamous cell carcinoma. The G-C and G-A haplotypes have a lesser distribution while the T-A haplotype is non-existent. The incidence of (G-C/T-C) diplotype is more important than the G-A haplotype in all the studied cases. Our results are strongly correlated with the data of Caucasian population.