Association of EGFR 1 Gene Alteration and their Association with Lung Adenocarcinoma Patients

Background: The epidermal growth factor receptor 1 (EGFR1) plays a significant role in cell proliferation anddevelopment. Its regulation in humans is very critical and incompletely understood in Non small cell lung cancer(NSCLC). Methods: 100 newly diagnosed NSCLC (lung adenocarcinoma) patients and 100 healthy controls wereincluded and allele specific (AS) polymerase chain reaction (PCR) was used to genotype and expression was analyzedby quantitative real time PCR. Overall survival of patients was analyzed by Kaplan-Meier method and for prognosticsignificance ROC curve was plotted. Results: A statistically significant difference (p<0.0001) in CC, AA and CAgenotypes distribution among patients and healthy controls was observed. Compared to the CC genotype as reference,OR was 30.40 (95%CI 1.75- 524.9, p=0.0002) and 3.97 (95%CI 1.49-10.52, p=0.003) for the homozygous AA andheterozygous CA genotypes respectively. Kaplan-Meier survival analysis was also performed to analyze the relationshipof EGFR1 (-191C/A) genotypes with progression free median survival of NSCLC patients and the difference wasfound to be significantly (p=0.0002) associated with different genotypes. In the ROC curve with respect to TNM stageat optimal cut-off value of 9.88 fold increase in EGFR1 mRNA expression, sensitivity and specificity were 92.9%,83.3% respectively (AUC=0.95, p<0.0001). ROC curve w.r.t. distant metastases at optimal cut-off value of 13.5 foldchange EGFR1 mRNA expression, sensitivity and specificity were 68.2%, 71.4% respectively (AUC=0.81, p<0.0001).In ROC curve w.r.t to presence/ absence of pleural effusion at optimal cut-off value of 14.8 fold change EGFR1mRNA expression sensitivity and specificity were 66.7%, 68.2% respectively (AUC=0.71, p=0.009). Conclusions:Study concluded EGFR1 promoter polymorphism could be a risk factor associated with disease and may be used asprognostic marker for patients’ survival and predictor for disease worseness.