Abstract A78: EGF+61 A>G polymorphism is not associated with lung cancer risk in Brazilian population

Abstract

Lung cancer is a malignancy with high incidence and mortality, being in Brazil the second most common cancer in men and the fourth in women. Epidermal growth factor (EGF) and its receptor (EGFR) play a central role in lung carcinogenesis, once EGF/EGFR interaction activates several intracellular pathways that control cellular growth, proliferation, differentiation, migration, and apoptosis. The association has been described between a single nucleotide polymorphism (SNP) in EGF promoter region (EGF+61 A>G – rs4444903) and cancer susceptibility to distinct tumors, including melanoma, gliomas, gastric cancer, hepatocellular carcinoma, and others. In lung cancer, the results are still scarce and unclear, with different reports showing discrepant results. Therefore, the aim of this study is to evaluate the risk of lung cancer development associated with the EGF+61 A>G SNP in a Brazilian population. For that, 437 lung cancer patients and 1104 controls were included in this study. Following DNA isolation from both tumor (FFPE) and controls (blood), the EGF+61 A>G genotype was assessed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP), and TaqMan Genotyping Assay, respectively. Statistical analysis included chi-square and Mann-Whitney tests, and logistic regression model to estimate Odds Ratios. As expected, uni- and multivariate analyses showed that tobacco consumption (p<0.001; OR=4.6; 95% CI 3.53-6.2 for smokers and p<0.001; OR 1.9; 95% CI 1.48-2.56 for ex-smokers) and age (p<0.001; OR=1.03; 95% CI 1.02-1.04 per year) were important risk factors for lung cancer. The genotype frequencies observed in lung cancer patients were 27.9% of AA, 45.1% of AG, and 20% of GG, and for controls were 25.3% of AA, 51.6% of AG, and 23.1% of GG. The allele frequencies were 51% of A and 49% of G in patients, and 50% of each allele in controls. Hardy-Weinberg equilibrium was estimated among patients and controls and no deviation was found in control group. However, patient's group revealed a p=0.039. No significant differences for the three genotypes (AA, AG, and GG) were observed between cases and controls (p=0.064; AG genotype: OR=0.79; 95% CI 0.605-1.033 and GG genotype: OR=1.05; 95% CI 0.78-1.43). We further grouped AG and GG genotypes and compared with the AA genotype, and also did not found significant differences (p=0.3; OR=0.87; 95% CI 0.681-1.120). Moreover, overall survival was calculated for patients considering AG/GG versus AA genotypes, and no significant differences were observed (p=0.21). In conclusion, the present study suggests that EGF+61 A>G polymorphism is not a risk factor for lung cancer in the Brazilian population. Citation Format: Ana Carolina Laus, Flavia Escremim de Paula, Marcos Alves de Lima, Carolina Dias Carlos, Izabela Natalia Faria Gomes, Pedro Rafael Martins de Marchi, Luciano de Souza Viana, Rui Manuel Vieira Reis. EGF+61 A>G polymorphism is not associated with lung cancer risk in Brazilian population [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A78.