Abstract Lung cancer is a malignancy with high incidence and mortality worldwide, being in Brazil the first most lethal cancer in men and second 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. It has been described the association between a single nucleotide polymorphism (SNP) in EGF promoter region (EGF+61 A>G - rs4444903) and cancer susceptibility to distinct tumors. 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 the Brazilian population. For that, 669 lung cancer patients and 1104 controls were analyzed. Following DNA isolation from both cases (FFPE or blood) and controls (blood), the EGF+61 A>G genotype was assessed by PCR-RFLP in FFPE samples, and TaqMan genotyping assay for blood's DNAs. As expected, uni- and multivariate analyses, showed that tobacco consumption (p<0.001; OR=11.47; 95% CI 8.44-15.58 for smokers and p<0.001; OR 3.06; 95% CI 2.28-4.10 for ex-smokers) and age (p<0.001; OR=3.74; 95% CI 1.2.95-4.74 for >65 years) were important risk factors for lung cancer. Both patients and controls were in Hardy-Weinberg equilibrium. The genotype frequencies observed in lung cancer patients were 27.4% of AA, 47.4% of AG and 25.3% of GG, and for controls were 25.3% of AA, 51.6% of AG and 23.1% of GG. The allele frequencies were 51.1% of A and 48.9% of G in patients for both cases and controls. No significant differences for the three genotypes (AA, AG and GG - model 1) were observed between cases and controls (p=0.116; AG genotype: OR=0.80; 95% CI 0.61-1.05 and GG genotype: OR=1.03; 95% CI 0.75-1.42). We further grouped AG and GG and compared with the AA genotype (model 2), as well grouped AA and AG, compared to GG genotype (model 3), and no significant differences were found (model 2 - p=0.3; OR=0.87; 95% CI 0.67-1.12; model 3 - p=0.197; OR= 1.19; 95% CI 0.91-1.55). Moreover, disease-free and overall survivals were calculated considering the 3 models, and no significant differences were observed. In conclusion, the present study suggest that EGF+61 A>G polymorphism is not a risk factor for lung cancer in Brazilian population. Citation Format: Ana C. Laus, Flavia E. de Paula, Marcos A. Lima, Carolina D. Carlos, Izabela N. Gomes, Pedro R. de Marchi, Luciano S. Viana, Cristovam Scapulatempo Neto, Rui M. Reis. EGF+61 A>G polymorphism is not a lung cancer risk: A case-control study in a large Brazilian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1406.