Investigating the importance of EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer as potential diagnostic biomarker in Iranian population

Abstract Background In Iran, lung cancer is the third most common type of cancer and its prevalence is increasing rapidly. Identification informative genetic polymorphisms in cancer causing genes including epidermal growth factor receptor (EGFR) as key gene in control of cellular proliferation via intrinsic tyrosine/kinase activity, exonuclease 1 (EXO1) as one of the upregulated gene in different human malignancies and leptin (LEP) participate in carcinogenesis in lung cancer appears to be used as potential genetic markers for predicting lung cancer risk. There is no study about investigate association of the EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer in Iranian population. The aim of this study was investigating the association of EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer as a potentially diagnostic biomarker in Iranian population. Methods In this case–control study, A total of 100 patients with lung cancer and 100 age and gender-matched healthy controls were recruited into this study and the association between EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with the risk of lung cancer was investigated by using PCR–RFLP technique and bioinformatics approach. Results The rs712829 of EGFR gene show that a significant statistical difference between G allele and risk of lung cancer (P = 0.001, OR = 2.976, CI = 95%, 1.557–5.691), in contrast, the T allele and TT genotype show a protective role against the risk of lung cancer. Result of in silico analysis indicated that the rs712829 alter splicing and promoter regulation of EGFR gene and associated with the risk of lung cancer. PCR–RFLP result for rs1047840 of Exo1 gene showed that the AA genotype and A allele of this polymorphism associated with risk of lung cancer, whereas the GG genotype show a protective effect against the risk of lung cancer (P = 0.004, OR = 5.391, CI = 95%, 1.690–17.200). On the other hand, in silico analysis showed that the existence of rs1047840 in Exo1 gene influence lung cancer susceptibility. For rs7799039 of LEP gene, PCR–RFLP analysis showed that, there is no significant association between this polymorphism and the risk of lung cancer. Conclusion The rs712829 of EGFR gene and rs1047840 of Exo1 are associated with risk of lung cancer among Iranian population and can be used as a potentially candidate biomarker for early detection and primary prevention