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Association of a potential functional pre‐miR‐218 polymorphism and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk
Author(s) -
Han Yifang,
Pu Rui,
Han Xue,
Zhao Jun,
Li Weiping,
Yin Jianhua,
Zhang Yuwei,
Shen Qiuxia,
Xie Jiaxin,
Zhang Qi,
Jiang Shuang,
Li Juhong,
Zhang Hongwei,
Wang Hongyang,
Cao Guangwen
Publication year - 2014
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12313
Subject(s) - hepatocellular carcinoma , hbsag , hepatitis b virus , odds ratio , medicine , hepatitis b , genotype , gastroenterology , confidence interval , liver cancer , oncology , immunology , virus , biology , genetics , gene
Background & Aims 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.