***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Functional polymorphisms of miRNAs may affect the function and target expression of miRNAs , which can , in turn , affect the biological activity , etiology , and prognosis of cancer . We hypothesized that four common polymorphisms in pre-miRNAs ( hsa-mir-146a rs2910164 G > C , hsa-mir-196a2 rs11614913 C > T , hsa-mir-149 rs2292832 G > T , and hsa-mir-499 rs3746444 A > G ) are associated with survival in SCCNOP . We used univariate and multivariable Cox models to evaluate the associations between the four polymorphisms and survival . We found that hsa-mir-149 rs2292832 and hsa-mir-499 rs3746444 had statistically significant associations with survival , but hsa-mir-146a rs2910164 and hsa-mir-196a2 rs11614913 did not . Patients having the hsa-mir-149 CC and hsa-mir-499 TT wild-type genotypes had significantly better overall , disease-specific , and disease-free survival compared with those who had the corresponding variant CT/TT and CT/CC genotypes , respectively . Furthermore , these genotypes were significantly associated with reduced risk of overall death , death owing to disease , and recurrence after adjustment for important prognostic confounders , indicating that these pre-miRNA polymorphisms may be prognostic biomarkers for SCCNOP . Moreover , the stratified analyses based on smoking status and treatment indicated that the effects of hsa-mir-149 and hsa-mir-499 polymorphisms on survival were more pronounced in ever smokers and patients treated with chemoradiation . Our findings support that the hsa-mir-149 rs2292832 and hsa-mir-499 rs3746444 polymorphisms play a significant role in the prognosis of SCCNOP , especially in smokers and patients treated with chemoradiation . Prospect i ve studies with larger sample sizes are needed to confirm these findings To investigate the prognostic effect of microRNA single nucleotide polymorphisms ( SNP ) on non-small cell lung cancer ( NSCLC ) patients , 658 female participants from northeast China were enrolled in our prospect i ve cohort study and followed up from 2010 to 2015 . C-containing genotypes of miR-149 rs2292832 were associated with better overall survival ( OS ) . The joint effect of miR-149 and miR-196a2 and the joint effect of miR-149 and miR-608 were also observed in our study . To verify the function of miR-149 rs2292832 , A549 cell lines were stably transfected with lenti-virus containing miR-149-C vector , miR-149-T vector and empty vector . Cells containing C allele assumed a higher expression level of miR-149 , a decrease in cell growth and the sensitivity to anticancer drug when compared with cells containing T allele . The role of miR-149 playing in cancer prognosis may function through DNA topoisomerases 1 ( TOP1 ) pathway , according to the results from luciferase reporter assays . In conclusion , miR-149 C allele may be a prognostic biomarker for better NSCLC OS miRNAs play important roles in numerous cellular processes , including development , proliferation , apoptosis , and carcinogenesis . Because altered expression and function of miRNAs has been observed in bladder cancer , we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis . Using bioinformatics tools , we selected five single-nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA-disease associations in a two-stage model , consisting of 1,019 bladder cancer cases and 1,182 controls ( 683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set ) . We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets , as well as the combined set [ OR = 0.80 , 95 % confidence interval ( CI ) = 0.71 - 0.90 , P = 2.92 × 10(-4 ) ] . Furthermore , the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence , compared with the GG genotype ( P = 0.016 ) . Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and TRAF6 in bladder cancer cells . Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele ( P = 0.010 ) . Taken together , our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer , suggesting it may represent a biomarker for risk prevention and therapeutic intervention . Further larger and prospect i ve cohorts are needed to vali date our findings Background Esophageal squamous cell carcinoma ( ESCC ) is a deadly disease with a poor prognosis . The single nucleotide polymorphisms ( SNPs ) involved in microRNA ( miRNA ) functions are potential biomarkers for prognosis of various human cancers . We investigated the association of the miRNA-related SNPs with the prognosis of ESCC . Methods A total of 504 patients with ESCC were enrolled . The genotypes of 18 miRNA-related SNPs were analyzed from the genomic DNA of peripheral leukocytes and were correlated with the prognosis of patients r and omly assigned to a training set ( n = 129 ) or an independent replication set ( n = 375 ) . Results In the training group , only the rs4919510 SNP of the mir-608 gene was significantly associated with clinical outcome ( CG vs. GG , hazard ratio [ HR ] 0.47 , 95 % confidence interval [ CI ] 0.27–0.82 , P = 0.008 for death , HR 0.47 , 95 % CI 0.29–0.77 , P = 0.002 for recurrence ) . The association for overall survival was confirmed in an independent replication group ( CG vs. GG , HR 0.74 , 95 % CI 0.56–0.97 , P = 0.031 for death ) . Two other SNPs , rs14035 of RAN and rs7813 of GEMIN4 , showed a borderline significant association with the prognosis of ESCC . In a combined analysis , we demonstrated the cumulative effect of the mir-608 , RAN , and GEMIN4 polymorphisms on the clinical outcome of ESCC ( HR 1.40 , 95 % CI 1.18–1.67 , Ptrend < 0.001 for mortality , HR 1.30 , 95 % CI 1.10–1.53 , Ptrend = 0.002 for recurrence ) . The cumulative effect was more evident in patients receiving concurrent chemoradiotherapy . Conclusions The hereditary genetic polymorphisms of mir-608 , RAN , and GEMIN4 can serve as predictors for clinical outcome in ESCC patients treated with concurrent chemoradiotherapy MicroRNA-27a ( miR-27a ) is deemed to be an oncogene that plays an important role in development of various cancers , and single nucleotide polymorphism ( SNP ) of miR-27a can influence the maturation or aberrant expression of hsa-miR27a , result ing in increased risk of cancer and poor prognosis for non-small cell lung cancer ( NSCLC ) . This study aim ed to assess the effects of rs895819 within miR-27a on susceptibility and prognosis of NSCLC patients in 560 clinical confirmed cases and 568 healthy check-up individuals .  Adjusted odds/hazard ratios ( ORs/HRs ) and 95 % confidential intervals ( CIs ) were calculated to evaluate the association between rs895819 and the risk and prognosis of NSCLC . The results showed that allele A and genotype GG of rs895819 were significantly associated with an increased risk of NSCLC ( 38.9 % vs 30.8 % , adjusted OR=1.26 , 95%CI=1.23 - 1.29 for allele G vs A ; 18.1 % vs 11.7 % , adjusted OR=1.67 , 95%CI=1.59 - 1.75 for genotype GG vs AA ) . Moreover , positive associations were also observed in dominant and recessive models ( 53.7 % vs 49.9 % , adjusted OR=1.17 , 95%CI=1.13 - 1.20 for GG/AG vs AA ; 18.1 % vs 11.7 % , adjusted=1.65 , 95%CI=1.58 - 1.73 ) . However , no significant association was found between rs895819 and the prognosis of NSCLC in genotype , dominant and recessive models . These results suggested that miR-27a might be involved in NSCLC carcinogenesis , but not in progression of NSCLC . The allele G , genotype GG and allele G carrier ( GG/AG vs AA ) of rs895819 might be genetic susceptible factors for NSCLC . Further multi- central , large sample size and well- design ed prospect i ve studies as well as functional studies are warranted to verify our findings Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews 
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Results : We systematic ally review ed the association of 17 miRNAs SNPs with cancer prognosis including 24,721 sample s. It was shown that 6 miRNAs SNPs ( miR-608 rs4919510 , miR-492 rs2289030 , miR-378 rs1076064 , miR-499 rs4919510 , miR-149 rs2292832 , miR-196a2 rs11614913 ) were associated with better cancer overall survival ( OS ) while let-7i rs10877887 was associated with poor OS ; the homozygous and heterozygote genotype of miR-423 were related to poor cancer relapse-free survival ( RFS ) when compared with the wild genotype ; miR-146 rs2910164 was linked to favorable cancer DFS while miR-196a2 rs11614913 was associated with poor DFS .
Conclusions : In summary , let-7i rs10877887 , miR-608 rs4919510 , miR-492 rs2289030 , miR-378 rs1076064 , miR-423 rs6505162 , miR-499 rs4919510 , miR-149 rs2292832 , miR-146 rs2910164 , and miR-196a2 rs11614913 might serve as potential biomarkers for cancer prognosis