Background: Renal cell carcinoma represents 3% of all adult malignancies. MicroRNAs
exhibit specific functions in various biological processes through their interaction with cellular
mRNA involved in apoptosis and cell cycle control. Recent studies have reported the potential
association of single-nucleotide polymorphisms (SNPs) in miRNA-binding sites of VHL-HIF1α
pathway genes with renal cancer development and progression.
Objective: The objective of this study is to investigate the SNPs invoking an alteration in the nature
of interaction with miRNA binding sites of VHL-HIF1α pathway genes.
Methods: Total 450 cases of histologically and clinically verified ccRCC and 490 controls were included
in our study. Genotyping was performed using a TaqMan PCR allelic discrimination
method. Kaplan-Meier method of statistical analysis was implemented to analyze the overall patient
Results: Polymorphism rs10491534 in TSC1 gene was significantly associated with the risk of developing
advanced ccRCC. Allele G of rs1642742 in VHL gene was significantly prevalent in ccRCC
compared with the control group aged 55 and older (OR = 1.5566; CI [1.1532-2.1019]). Results
from the dominant model combining individuals with AG or AA genotype showed that the A
allele bearers of CDCP1 rs6773576 exhibited a higher risk of death compared to GG carriers (HR
3.93, 95% CI 1.76-17.21, log-rank P = 0.0033).
Conclusion: The present study delineated the association of miRNA binding site variants in VHL-
HIF1α pathway genes with the ccRCC risk, which may affect the clinical outcomes.