Genetic variations in microRNA-related genes are associated with survival and recurrence in patients with renal cell carcinoma.
We took a polygenic approach to evaluate the effects of 41 potentially functional single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs)-related genes on survival and recurrence among renal cell carcinoma (RCC) patients. During a median follow-up of 21.8 months, among 316 RCC patients, 64 died and 56 developed recurrence. In single-SNP analysis, we identified seven SNPs significantly associated with RCC survival and five SNPs with recurrence. The most significant associations were SNPs in GEMIN4 with the variant alleles of both rs7813 and rs910925 associated with 1.74-fold [95% confidence interval (CI) = 1.15-2.62] increased risk of death, whereas the variant allele of rs3744741 conferred a decreased risk of death [hazard ratio (HR) = 0.39; 95% CI = 0.19-0.77]. Several SNPs belonging to the pre-miRNA and were identified to be significantly associated with RCC recurrence. Haplotypes of DICER and DROSHA were also associated with altered patient survival and recurrence. More importantly, we observed cumulative effects of multiple SNPs on RCC survival. Compared with subjects carrying zero to two unfavorable genotypes, those carrying three to five and six and more unfavorable genotypes had an increased risk of death with a HR of 2.49 (95% CI = 1.24-5.00) and 6.66 (95% CI = 2.49-17.86), respectively, with significant dose-response trend (P for trend<0.001). As the first study of miRNA-related genetic polymorphisms on RCC clinical outcome, our results strongly suggested that miRNA-related SNPs may impact the recurrence and survival in RCC patients. Future investigation in larger populations and functional characterizations are necessary to validate these results.
Lin
Jie
J
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Horikawa
Yohei
Y
Tamboli
Pheroze
P
Clague
Jessica
J
Wood
Christopher G
CG
Wu
Xifeng
X
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D043244:Ribonuclease III / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics
C406815:GEMIN4 protein, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D017411:Ribonucleoproteins, Small Nuclear; C517918:DROSHA protein, human; D043244:Ribonuclease III