In:
Liver International, Wiley, Vol. 34, No. 5 ( 2014-05), p. 728-736
Abstract:
Micro RNA ‐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. Methods rs11134527 located at putative promoter region of pre‐miR‐218 was genotyped in 1012 healthy controls, 302 hepatitis B surface antigen ( HB sAg) seroclearance subjects and 2011 subjects with chronic HBV infection (1021 with HCC ) using quantitative PCR . HBV mutation was determined by sequencing. Results 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 HB sAg‐positive subjects ( OR = 1.23, 95% CI = 1.02–1.50) and HB sAg 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. Conclusion 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.
Type of Medium:
Online Resource
ISSN:
1478-3223
,
1478-3231
DOI:
10.1111/liv.2014.34.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2124684-1
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