Lung cancer is the deadliest cancer worldwide. The mutational frequency of EGFR and KRAS genes in lung adenocarcinoma varies worldwide per ethnicity and smoking. The impact of EGFR and KRAS mutations in Brazilian lung cancer remains poorly explored. Thus, we investigated the frequency of EGFR and KRAS mutations in a large Brazilian series of lung adenocarcinoma together with patients’ genetic ancestry, clinicopathological and sociodemographic characteristics. The mutational frequency of EGFR was 22.7% and KRAS was 20.4%. The average ancestry proportions were 73.1% for EUR, 13.1% for AFR, 6.5% for AME and 7.3% for ASN. EGFR mutations were independently associated with never-smokers, high-Asian ancestry, and better performance status. KRAS mutations were independently associated with tobacco exposure and non-Asian ancestry. EGFR -exon 20 mutations were associated with worse outcome. The Cox regression model indicated a worse outcome for patients whose were older at diagnosis (>61 y), solid histological subtype, loss of weight (>10%), worse performance status (≥2), and presence of KRAS mutations and EGFR mutational status in TKi non-treated patients. In conclusion, we assessed the clinicopathological and ethnic impact of EGFR and KRAS mutations in the largest series reported of Brazilian lung adenocarcinomas. These findings can support future clinical strategies for Brazilian lung cancer patients.

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IntroductionThe Phelan–McDermid syndrome is a chromosomal disorder consisting of a selection on chromosome 22q13.3 associated psychiatric and emotional level, behavioral and traits of autism spectrum disorders. During the neurodevelopmental such chromosomal deletion, which associated with haplo insufficiency Shank 3 causes alterations in the synaptogenesis altering the balance of activating and inhibitory transmission. Throughout the various studies, it is considered that this syndrome has a psychiatric disorder bipolar like.Case presentationHere, we present s 13-year-old female diagnosed with autism spectrum disorders in childhood and presented regression with catatonia features and behavioral disorders. Interestingly, she presented mutation/microdeletion of the SHANK3 gene, inducing a premature stop codon in exon 21. Different pharmacological treatments (antipsychotics at high doses and benzodiazepines) failed to improve clinical symptoms and lead to multiple adverse events. In contrast, lithium therapy reversed clinical regression, stabilized behavioral symptoms and allowed patients to recover their pre-catatonia level of functioning. After the first menstruation there was a cycling psychiatric worsening with a similar clinical pattern so risperidone as adjunctive therapy. As a result of this, this patient recovered clinical and socio-functional stability.ConclusionsThey are previous cases where there affective and behavioral improvement after use of mood stabilizer molecules such as valproate or lithium. There is also evidence of the benefit of risperidone low to have a beneficial effect on the balance of activatory and inhibitory transmission level doses of NMDA receptors.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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.

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