Identification of miR-423 and miR-499 polymorphisms on affecting the risk of hepatocellular carcinoma in a large-scale population.
OBJECTIVE
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 (χ(2)=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.
1 Ministry of Education Key Laboratory of Contemporary Anthropology, Fudan University , Shanghai, China .
Yanyun
Y
Ma
Rui
R
Wang
Jun
J
Zhang
Wenshuai
W
Li
Chunfang
C
Gao
Jie
J
Liu
Jiucun
J
Wang
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D014408:Biomarkers, Tumor; C548900:MIRN423 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs