Though SNPs in miRNAs have been widely studied, the association between SNPs in miRNAs and renal cell cancer risk remains still unknown. Horikawa et al. defined 7 SNPs in 7 premiRNAs, and 10 SNPs in 8 pri-miRNAs, but none of them had a significant influence on RCC risk. Nevertheless, Horikawa et al. suggested that genetic polymorphisms of the miRNA-machinery genes might Z-VAD-FMK cost affect jointly To our knowledge, many human miRNA transcripts have target sequences in the 39-UTR to which miRNAs bind and exert posttranscriptional repression. Liu et al. found miR-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin and Chintharlapalli et al. suggested that oncogenic miR-27a was a target for anticancer agent in colon cancer cells. Our results showed that the wild genotype AA of pre-miR-27a had higher frequency in cases than in controls, whereas individuals carrying variant G allele had a reduced RCC risk, indicating that miR-27a was more likely to be an oncogene, which was consistent with previous studies. Mertens-Talcott et al. reported that in breast cancer cells, transfection of antisense miR-27a lead to increased expression ZBTB10 and these responses were accompanied by decreased expression of survivin, Moreover, survivin is a structurally unique member of the inhibitor of apoptosis protein family that suppresses apoptosis and regulates cell division. Despite the redundancy of cell death pathways, survivin appears to be required for cancer cell viability, and interference with survivin expression/function has been associated with catastrophic defects of mitotic transition and induction of mitochondrial-induced cell death. Over-expression of survivin mRNA and protein were detected in RCC cell lines but not in normal human kidney epithelial cell line. Elevated expression of survivin was also observed in RCC tissues compared with adjacent normal tissues. RCC patients with high survivin levels had a significantly shorter overall survival time than those with low levels. In other words, decreased miR-27a levels might reduce the incidence of RCC through suppressing the expression of survivn indirectly. That was why we focus on the pre-miR-27a polymorphism in RCC patients. In this study, there were more hypertension patients and diabetics among the cases than among the controls, indicating that there was potential association between the two factors and RCC. We also found that rs895819 had multiplicative interactions with hypertension. It has been reported that certain types of renal tumors and cancer treatment could cause hypertension and a history of diabetes has been linked to renal cell cancer risk in several cohort studies, but its role independent of those of obesity and hypertension has not been demonstrated conclusively. Besides, our results indicated that the individuals with G allele have a reduced RCC risk in non-smokers. Cigarette smoking is the most consistently established causal risk factor for RCC, accounting for approximately 20% of cases of RCC. Compared to never smokers, risk increased about 50% in male and 20% in female smokers. Furthermore, after stratification for RCC clinical stage, it appeared that rs895819 GG genotype had a decreased risk of RCC with localized clinical stage. Thus, it was plausible that the variation was involved in the lower stage RCCs. However, this hypothesis needs to be confirmed in further studies. As to the association between genotypes and overall survival of RCC, there was no significant result.