Abstract 1350: Genetic variations in apoptosis pathway are associated with survival in late stage non-small cell lung cancer.

Abstract

Abstract Dysregulation of apoptosis pathway plays an essential role in carcinogenesis, tumor progression, and resistance to chemotherapy. We hypothesized that genetic variations in genes involved in the apoptosis pathway may affect the survival in late stage non-small cell lung cancer (NSCLC) patients. To test this hypothesis, we genotyped 583 tagging SNPs in 598 late stage NSCLC patients and analyzed their associations with survival individually and jointly. Seven SNPs were statistically significantly associated with overall survival after correction for multiple comparisons (q<0.1). The most significant SNP was rs17592236 on FOXO1 gene under the dominant model (OR: 2.54, 95%CI: 1.71-3.78, p=4.15x10−6). We also observed a significant cumulative effect. Compared to the reference group (patients with no more than two risk alleles), those having five or more risk alleles were much more likely to die within seven months (HR: 3.58, 95% CI: 2.55-5.04, p<0.001). Notably, the median survival time (MST) was significantly reduced by up to 15 months in high risk patients when compared to the reference group (MST: 22.2 months, p<0.001). Survival tree analysis revealed potential higher order gene-gene interactions among these SNPs. Our results provided evidence that genetic variations in the apoptosis pathway modulate NSCLC survival and may serve as biomarkers to differentiate NSCLC patients with different prognosis. Citation Format: Xiang Shu, Charles Lu, Joe Y. Chang, Jack A. Roth, Xifeng Wu. Genetic variations in apoptosis pathway are associated with survival in late stage non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1350. doi:10.1158/1538-7445.AM2013-1350