Significance Estimation of EGFR and Their Polymorphisms - 216G>T (rs712829), -191C>A (rs712830) and 181946C>T (D994D) (rs2293347) in Non-Small Cell Lung Cancer

Abstract

Hypothesis: Epidermal growth factor receptor (EGFR) was usually over expressed in many epithelial cancers including lung cancer. It is trigger molecule for many important processes in normal cells concerning growth, development, differentiation, but in tumor cells it conduct many abnormal messages through signaling network cascade leading to cancer genesis. Objectives: Genetic and epigenetic changes in lung cancer, including single nucleotide polymorphisms (SNPs) are in the course of scientific interest with many reasons. Methods: Here we described methods for standardization of PCR reaction including different additives, temperature and other conditions, for estimation of expression of promoter regulators of EGFR, including - 216G>T, -191C>A and 181946 C>T (SNPs) in 47 NSCLC patients in comparison to 43 health persons in Serbia. These data where compared with results obtained in different ethnic populations. Result: Significant differences in EGFR and SNPs distributions were noticed through great ethnic populations. These results showed that the most frequent haplotypes in both NSCLC patients and healthy subjects in Serbia were CG (54.96 %), CT (27.36 %), while AG (16.38 %) and AT where present at 1.30 %. Caucasians and Afro-Americans had more frequent -216G/T than Asians, but -191C/Awas present only in Caucasians. SNPs -216G>Tand -191C>A discussed here, were present with different frequency in great ethnic groups. Conclusions: Still it is unclear relation between those polymorphisms and common mutations, but they were connected with enhanced EGFR promoter activity, with increased gene and protein expression, and some side effects of TKI used for NSCLC. According to those considerations, it could be noticed that investigation of SNPs could be potential pharmacogenetic biomarker for efficacy and safety of TKI treatment approach for NSCLC.