MicroRNAs (miRNAs) play an important role in carcinogenesis through the 
regulation of their target genes. miRNA-related single nucleotide polymorphisms 
(miR-SNPs) can affect miRNA biogenesis and target sites and can alter microRNA 
expression and functions. We examined 11 miR-SNPs, including 5 in microRNA 
genes, 3 in microRNA binding sites and 3 in microRNA-processing machinery 
components, and evaluated time to recurrence (TTR) according to miR-SNP 
genotypes in 175 surgically resected non-small-cell lung cancer (NSCLC) 
patients. Significant differences in TTR were found according to KRT81 rs3660 
(median TTR: 20.3 months for the CC genotype versus 86.8 months for the CG or GG 
genotype; P = 0.003) and XPO5 rs11077 (median TTR: 24.7 months for the AA 
genotype versus 73.1 months for the AC or CC genotypes; P = 0.029). Moreover, 
when patients were divided according to stage, these differences were maintained 
for stage I patients (P = 0.002 for KRT81 rs3660; P<0.001 for XPO5 rs11077). 
When patients were divided into sub-groups according to histology, the effect of 
the KRT81 rs3660 genotype on TTR was significant in patients with squamous cell 
carcinoma (P = 0.004) but not in those with adenocarcinoma. In the multivariate 
analyses, the KRT81 rs3660 CC genotype (OR = 1.8; P = 0.023) and the XPO5 
rs11077 AA genotype (OR = 1.77; P = 0.026) emerged as independent variables 
influencing TTR. Immunohistochemical analyses in 80 lung specimens showed that 
95% of squamous cell carcinomas were positive for KRT81, compared to only 19% of 
adenocarcinomas (P<0.0001). In conclusion, miR-SNPs are a novel class of SNPs 
that can add useful prognostic information on the clinical outcome of resected 
NSCLC patients and may be a potential key tool for selecting high-risk stage I 
patients. Moreover, KRT81 has emerged as a promising immunohistochemical marker 
for the identification of squamous cell lung carcinoma.