Association of a potential functional pre-miR-218 polymorphism and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk.
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.


METHODS
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.


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 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.


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.
['Han|Yifang|Y|', 'Pu|Rui|R|', 'Han|Xue|X|', 'Zhao|Jun|J|', 'Li|Weiping|W|', 'Yin|Jianhua|J|', 'Zhang|Yuwei|Y|', 'Shen|Qiuxia|Q|', 'Xie|Jiaxin|J|', 'Zhang|Qi|Q|', 'Jiang|Shuang|S|', 'Li|Juhong|J|', 'Zhang|Hongwei|H|', 'Wang|Hongyang|H|', 'Cao|Guangwen|G|']
D000328:Adult D000368:Aged D006528:Carcinoma, Hepatocellular D016022:Case-Control Studies D005260:Female D005814:Genes, Viral D020022:Genetic Predisposition to Disease D005838:Genotype D006515:Hepatitis B virus D019694:Hepatitis B, Chronic D006801:Humans D008103:Liver Cirrhosis D008113:Liver Neoplasms D008297:Male D035683:MicroRNAs D008875:Middle Aged D009154:Mutation D020641:Polymorphism, Single Nucleotide D018570:Risk Assessment D014779:Virus Replication
hepatitis B virus mutation hepatocellular carcinoma miR-218 polymorphysims