Abstract A3: MicroRNA-related polymorphisms are associated with clinical outcomes in early stage non-small cell lung cancer patients

Abstract

Abstract MicroRNAs (miRNA) can function as oncogenes or tumor suppressors. In this study, to test the hypothesis that genetic variation within miRNA processing genes or miRNA binding sites on cancer-related genes may alter clinical outcomes in non-small cell cancer (NSCLC) patients, we genotyped 77 single nucleotide polymorphisms (SNPs) from eight miRNA processing genes and 163 SNPs from 133 predicted miRNA binding sites in 598 patients with early stage (stage I, IIA and IIB) NSCLC to determine the effect of these variations on progression risk and overall survival. We further conducted a subset analysis to exclude potential bias due to different treatment regimens. We identified 37 SNPs associated with overall survival. In the surgery-only patients, 22 SNPs modulated overall survival, including FZD4:rs713065 that remained significant for decreased risk after multiple comparisons (HR: 0.53, 95% CI: 0.36–0.77). For progression risk, 21 and 25 SNPs were found to be significant in the entire and surgery-only patient populations, respectively. Following multiple comparison, ICAM1:rs281437 (HR: 1.80, 95% CI: 1.29–2.52) and MDM4:rs10900596 (HR: 2.01, 95% CI: 1.26–3.19) remained significant increase in progression risk, while FAS:rs2234978 (HR: 0.58, 95% CI: 0.41–0.80) displayed a significantly protective effect. CDC7:rs12125947 (HR: 2.19, 95% CI: 1.37–3.51) remained significant risk effect in the surgery-only patients. A strong cumulative, dose-effect of these variant genotypes to increase risk and dramatically decrease median event-free time was consistently observed. We also identified potential higher-order gene-gene interactions among these SNPs. With validation, our result can be used in the prognosis of clinical outcomes for early stage NSCLC patients. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A3.