The prognostic impact of microRNA sequence polymorphisms on the recurrence of patients with completely resected non-small cell lung cancer

Objectives: MicroRNAs (miRNAs) are widely known for their function as regulators of gene expression via translational repression. Polymorphisms in miRNAs have been shown to affect the regulatory capacity of miRNAs by influencing miRNA processing and/or miRNA-mRNA interactions. The purpose of this study was to investigate the association between 7 single nucleotide polymorphisms (SNPs) commonly found in precursor miRNA (pre-miRNA) and primary miRNA (pri-miRNA) sequences and the recurrence of disease in patients who underwent a complete resection of non-small cell lung cancer (NSCLC). Methods: Five SNPs found in pre-miRNAs (rs11614913/miR-196a2, rs2910164/miR-146a, rs6505162/miR-423, rs2289030/miR-492, and rs895819/miR-27a) and 2 SNPs found in pri-miRNAs (rs7372209/miR-26a-1 and rs213210/miR-219-1) were genotyped in 388 patients with NSCLC. Results: Among 388 patients, variants of the rs2910164 SNP were significantly associated with recurrence-free survival (RFS) (P = .016, log-rank test). When the results were subdivided by the tumor stage, variants of the rs2910164 and rs11614913 SNPs positively correlated with a better RFS (adjusted hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.28-0.80; adjusted HR, 0.60; 95% CI, 0.38-0.94, respectively) in patients with stage II and stage III disease. Moreover, RFS significantly improved in patients with higher numbers of variant alleles in the rs2910164 and rs11614913 SNPs. Conclusions: Our findings suggest that polymorphisms in the rs2910164 of miR-146a and the rs11614913 of miR-196a2 are associated with prognosis in patients with completely resected NSCLC. (J Thorac Cardiovasc Surg 2012; 144: 794-807)