Data from MicroRNA-Related Genetic Variants Associated with Clinical Outcomes in Early-Stage Non–Small Cell Lung Cancer Patients

Given the density of single-nucleotide polymorphisms (SNP) in the human genome and the sensitivity of single-nucleotide changes in microRNA (miRNA) functionality and processing, we asked whether polymorphisms within miRNA processing pathways and binding sites may influence non–small cell lung cancer (NSCLC) patients' prognosis. We genotyped 240 miRNA-related SNPs in 535 patients with stage I and II NSCLCs to determine associations with overall recurrence and survival as well as effect in specific treatment subgroups. After correcting for multiple comparisons, the G allele of FZD4:rs713065 displayed a significant association with decreased risk of death in surgery-only patients [HR, 0.46; 95% confidence interval (CI), 0.32–0.65]. DROSHA:rs6886834 variant A allele (HR, 6.38; 95% CI, 2.49–16.31) remained significant for increased risk of recurrence in the overall and surgery-only populations, respectively. FAS:rs2234978 G allele remained significantly associated with survival in all patients (HR, 0.59; 95% CI, 0.44–0.77), whereas borderline significant in subgroups (surgery-only: HR, 0.59; 95% CI, 0.42–0.84; surgery plus chemo: HR, 0.19; 95% CI, 0.07–0.46). Luciferase assays showed that the FAS SNP created a miR-651 functional binding site. Survival tree analysis was conducted to classify patients into distinct risk subgroups based on their risk genotype combinations. These results indicate that miRNA-related polymorphisms may be associated with NSCLC patients' clinical outcomes through altered miRNA regulation of target genes. Cancer Res; 73(6); 1867–75. ©2013 AACR.