Identification of miR-423 and miR-499 Polymorphisms on Affecting the Risk of Hepatocellular Carcinoma in a Large-Scale Population

摘要

Aims: MicroRNAs (miRNAs) regulate gene expression and act as tumor suppressors or enhancers in oncogenesis. Single-nucleotide polymorphisms (SNPs) in miRNAs could alter the processing or actions of mature miRNA. So far, the association of miR-423 rs6505162 with cancers has not been explored, while the association of miR-499 rs3746444 was only reported in small-sized samples of different types of populations. Methods: To evaluate the association of miR-499 rs3746444 and miR-423 rs6505162 with hepatocellular carcinoma (HCC), we performed a large-scale case-control study of 984 patients with HCC and 991 cancer-free controls. Results: The risk of HCC was significantly higher with miR-499 rs3746444 TC+CC genotypes compared with those with the TT genotype (odds ratio [OR]=1.372, 95% confidence intervals [CI]=1.099–1.713, p=0.005), as was the risk of hepatitis B virus-related HCC (OR=1.437, 95% CI=1.128–1.831, p=0.003). Moreover, subjects with the TC+CC genotypes were more vulnerable to advanced HCC with larger tumor size (χ²=13.014, p=0.001) and/or higher total bilirubin (p=0.004), which suggested that a TT genotype or T allele might serve as a protective factor. miR-423 rs6505162 had no effect on the risk of HCC. Conclusions: miR-499 rs3746444 may contribute to the risk and prognosis of HCC, indicating that this SNP could be developed as a biomarker for HCC prediction.