IntroductionPolymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population.Materials and MethodsBlood from patients with NSCLC was prospectively collected. To perform an association study, DNA from these patients and healthy controls were genotyped for a panel of 19 SNPs using a Sequenom® MassARRAY platform. Kaplan-Meier curves were used to assess the overall survival (OS) and progression-free survival (PFS).ResultsOne hundred and forty-four patients with NSCLC were successfully consecutively genotyped for the 19 SNPs. One SNP was associated with NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology: rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF –460) C/T and rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p = 0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p = 0.042; rs3025010 (VEGF intron 5 C/T), p = 0.047; rs401681 C/T at 5p15, p = 0.046; and rs31489 C/A at 5p15, p = 0.029.ConclusionsOur study suggests that SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of patients may improve NSCLC screening strategies and therapeutic management as well.

e19069 Background: Our purpose was to evaluate epidermal growth factor (EGF) +61 A/G polymorphisms as prognostic marker for progression free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC). Methods: 148 Portuguese Caucasian, medically treated for NSCLC between February 2010 and April 2011, were included in this study. DNA was extracted from peripheral blood leucocytes. Genotyping was performed by PCR-RFLP. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of selected polymorphisms. Results: Genotype frequency was A/A (25.3%), A/G (55.6%), G/G (19.2%). We found no differences in PFS among EGF+61 A/G polymorphisms and NSCLC (p = 0.339). However in G/G+A/G genotype patients group showed a trend to higher OS than A/A genotype (p = 0.055). Moreover, adenocarcinoma and squamous cell (SC) lung cancers patients harboring in A/G+G/G genotype group showed a trend to higher OS than those harboring A/A genotype (p = 0.074). Furthermore, patients in advanced stages carrying G/G genotype presented higher OS than those carrying A/A genotype: 13 months versus 3 months (adenocarcinoma); and 6 months versus 1 month (SC lung cancer), respectively, p = 0.043. Conclusions: We were able to observe the G/G genotype of EGF+61 A/G polymorphisms as a positive predictor for survival in medically treated advanced adenocarcinoma and squamous cell lung carcinoma patients. In future, our findings could be used as a biological marker in order to identify eligible NSCLC subgroups with potential improved response to EGFR tyrosine-kinase-inhibitors.