Both authors contributed equally to this study.
Association of a potential functional pre-miR-218 polymorphism and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk
Article first published online: 1 OCT 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 34, Issue 5, pages 728–736, May 2014
How to Cite
Liver Int. 2014: 34: 728–736
- Issue published online: 8 APR 2014
- Article first published online: 1 OCT 2013
- Accepted manuscript online: 5 SEP 2013 10:07PM EST
- Manuscript Accepted: 29 AUG 2013
- Manuscript Received: 23 JAN 2013
- National Natural Science Foundation of China. Grant Numbers: 81025015, 91129301, 30921006, 30901272
- National Major S&T Project. Grant Number: 2012ZX10002-008
- Shanghai R&D. Grant Number: 12GWZX0102
- hepatitis B virus;
- hepatocellular carcinoma;
Background & Aims
MicroRNA-218 (miR-218) can function as a tumour suppressor and inactivate cancer-promoting inflammation. However, role of miR-218 on hepatocellular carcinoma (HCC) remains unclear. To determine the contribution of miR-218 genetic predisposition and its interaction with hepatitis B virus (HBV) mutations to HCC risk.
rs11134527 located at putative promoter region of pre-miR-218 was genotyped in 1012 healthy controls, 302 hepatitis B surface antigen (HBsAg) seroclearance subjects and 2011 subjects with chronic HBV infection (1021 with HCC) using quantitative PCR. HBV mutation was determined by sequencing.
rs11134527 variant genotypes in dominant model was associated with HCC risk compared with all HCC-free subjects [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.04–1.43], HCC-free HBsAg-positive subjects (OR = 1.23, 95% CI = 1.02–1.50) and HBsAg seroclearance subjects (OR = 1.45, 95% CI = 1.08–1.96), adjusting for age and gender, and also associated with the generation of HBV preS deletion in men (adjusted OR = 1.85, 95% CI = 1.23–2.76). In multivariate regression analyses, rs11134527 in dominant model was associated with HCC risk (OR = 1.50, 95% CI = 1.05–2.13), whereas its multiplicative interaction with viral mutation T1674C/G was inversely associated with HCC risk (OR = 0.44, 95% CI = 0.21–0.96), adjusting for covariates including HBV mutations in the enhancer II-precore region; its interaction with HBV preS1 start codon mutation was associated with HCC risk (OR = 4.44, 95% CI = 1.27–15.55), adjusting for covariates including HBV mutations in the preS region.
rs11134527 may be a novel genetic risk factor of HCC in HBV-exposed subjects, can facilitate HBV preS deletion generation and predispose the host to the effect of T1674C/G and preS1 start codon mutation in hepatocarcinogenesis.