STRA6 mutations have been associated with severe pathologic phenotypes in multiple human organs, including the eye, brain, heart and lung. In this study, we analyzed the presence of two polymorphisms in patients with diagnosis of lung cancer in advanced stage. Patients consecutive, nonselected, pathologically confirmed with advanced NSCLC, who visited the Thoracic Oncology Unit at the Instituto Nacional de Cancerología from January 2014 to December 2015, were enrolled. Genomic DNA was obtained from peripheral blood. RT-PCR was used to genotype the different allelic variant. The SNPs, NC_000015.10:g.74194695T>A (rs351224) and NC_000015.10:g.74194103C>T (rs974456) were genotyped with commercially available TaqMan-validated SNP assays (C_3152256_10 and C_3152257_20, respectively). An allelic discrimination plot was used to identify individual genotypes. Subsequently, each allelic variant was confirmed by direct sequencing in 5% of the samples. All statistical analyses were carried out using the SPSS software package, v. 15 (SPSS Inc, Chicago, IL). This study included 145 patients, of whom 55.2% (80/145) were female. The mean age at diagnosis was 60.8 + 12.9 years. Around half of the patients had a tobacco history (52%) and 47% wood smoke exposure; most patients had a good performance status (≤ 1) (68%). Adenocarcinoma was the most common histologic subtype (83%). Approximately 15% of patients were known to have diabetes and at least 25% had a fasting glycemia upper of 126 mg/dL. Seventy-seven percent of patients received chemotherapy (QT) and 35.8% received treatment with TKIs, with a global response rate of 13% and 46%, respectively. We analyzed the frequency of the STRA6 SNPs in our population; we found a frequency of SNP1 (rs351224) of 0.503, 0.393 and 0.103, for wild-type homozygous patients (AA), heterozygous (AT), and variant homozygous (TT), respectively, whereas the frequency found for SNP2 (rs974456) was 0.352 for wild-type homozygous patients (CC), 0.531 for heterozygous (CT) and 0.117 for variant homozygous (TT). We analyzed the relationship between clinical characteristics and the polymorphism presence. According to our data, the absence of SNP2 was associated with response rate at QT (33% vs. 0%, p= 0.022), and patients with this polymorphism had glycemia below to 120 mg/dL (27.1% vs. 6.3%, p=0.068). No other clinicopathologic characteristics were found associated with the presence of any SNP. The overall survival of our patients was 15.5 months (10.6-20.3 months). We found a bordering difference in relation to SNP2 presence (presence vs. absence) (23.1 vs. 12.9 months, p=091). Other factors associated with a better OS were female gender (18 vs. 11 m, p=0.025), age <60 y (18 vs. 12 m, p=0.05), no tobacco history (23 vs. 10 m, p =0.021), and ECOG <2 (23 vs. 6 m, p < 0.001). We can suggest that the presence of SNP2 could be related to a better response to QT and better OS in our population.
Citation Format: Sae Muniz-Hernandez, Laura-Alejandra Ramírez-Tirado, Oscar Arrieta. Study of polymorphisms in stra6 in Mexican population with non-small cell lung cancer [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 5439.