Effect of a functional polymorphism in the pre-miR-146a gene on the risk and prognosis of renal cell carcinoma.

ABSTRACT

MicroRNAs (miRNAs) are non-coding RNAs that function as regulators of tumor suppressors and oncogenes. A G>C polymorphism (rs2910164) in the miR­146a precursor sequence leads to a functional change associated with a risk for various types of malignancy. The role of this single nucleotide polymorphism in the pathogenesis of renal cell carcinoma (RCC) has not yet been examined. The present study evaluated the association between rs2910164 genotypes and the risk and prognosis of RCC in a population comprised of 421 RCC cases and 432 controls. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for rs2910164 genotypes according to case status. Cox proportional hazards regression modeling was used to estimate hazards ratios and 95% CIs according to the genotypes among the RCC patients. It was found that the rs2910164 GG and GC genotypes were associated with an increased risk of RCC only in senior subjects (>57­years old; adjusted OR=1.59, 95% CI=1.04­2.43). Furthermore, the GC and GG genotypes were associated with a poorer survival rate among patients with RCC compared with the CC genotype (P=0.002). In conclusion, the observed association between the GG and GC genotype and poorer survival rate of RCC was at least partially mediated by the decreased expression of miR-146a.