Associations of pri-miR-34b/c and pre-miR-196a2 polymorphisms and their multiplicative interactions with hepatitis B virus mutations with hepatocellular carcinoma risk.
Associations of pri-miR-34b/c and pre-miR-196a2 polymorphisms and their multiplicative interactions with hepatitis B virus mutations with hepatocellular carcinoma risk.
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DOI：
10.1371/journal.pone.0058564
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cao G
中科院分区：
文献类型：
--
作者：
Han Y;Pu R;Han X;Zhao J;Zhang Y;Zhang Q;Yin J;Xie J;Shen Q;Deng Y;Ding Y;Li W;Li J;Zhang H;Cao G
pri-miR-34 b/c和pre-miR-196 a2基因多态性与癌症易感性相关。然而，这些多态性及其与B型肝炎病毒（HBV）突变的相互作用对肝细胞癌（HCC）发生的影响在很大程度上仍然未知。我们推测这些多态性可能与HBV突变相互作用，并在肝癌发生中发挥作用。 使用定量PCR对3,325例受试者（包括1,021例HBV-HCC患者）的Pri-miR-34 b/c rs 4938723（T>C）和pre-miR-196 a2 rs 11614913（T>C）进行基因分型。通过直接测序确定HBV突变。采用多变量回归分析评估多态性及其与性别或HCC相关HBV突变的相互作用对HCC风险的贡献。与HBV自然清除受试者相比，rs 4938723 CC基因型与HCC风险显著相关，经年龄和性别校正（校正比值比[AOR]= 2.01，95%置信区间[CI]= 1.16-3.49）。 与女性健康对照（AOR = 1.85，95%CI = 1.20-2.84）或女性无肝癌受试者（AOR = 1.62，95%CI = 1.14-2.31）相比，显性模型中的rs 4938723变异基因型显着增加了女性的肝癌风险。 rs 4938723 CC基因型和rs 11614913 TC基因型分别与HCC相关HBV突变T1674 C/G和G1896 A频率增加显著相关。rs 11614913与HCC风险无显著相关性，但其CC基因型显著增强了rs 4938723在女性中的作用。在多变量回归分析中，rs 4938723在显性模型中增加了HCC风险（AOR = 1.62，95%CI = 1.05-2.49），而其与C1730 G（一种与HCC风险负相关的HBV突变）的乘法相互作用降低了HCC风险（AOR = 0.34，95%CI = 0.15-0.81）; rs 11614913加强了G1896 A对HCC风险的影响，但减弱了A3120 G/T对HCC风险的影响。 rs 4938723可能是HCC的一个遗传危险因子，但其对HCC的影响受HBV基因突变的影响。rs 11614913可能不是HCC的易感因素，但它可能影响HBV突变或rs 4938723对HCC风险的影响。
Genetic polymorphisms of pri-miR-34b/c and pre-miR-196a2 have been reported to be associated with the susceptibility to cancers. However, the effect of these polymorphisms and their interactions with hepatitis B virus (HBV) mutations on the development of hepatocellular carcinoma (HCC) remains largely unknown. We hypothesized that these polymorphisms might interact with the HBV mutations and play a role in hepatocarcinogenesis. Pri-miR-34b/c rs4938723 (T>C) and pre-miR-196a2 rs11614913 (T>C) were genotyped in 3,325 subjects including 1,021 HBV-HCC patients using quantitative PCR. HBV mutations were determined by direct sequencing. Contributions of the polymorphisms and their multiplicative interactions with gender or HCC-related HBV mutations to HCC risk were assessed using multivariate regression analyses. rs4938723 CC genotype was significantly associated with HCC risk compared to HBV natural clearance subjects, adjusted for age and gender (adjusted odds ratio [AOR] = 2.01, 95% confidence interval [CI] = 1.16–3.49). rs4938723 variant genotypes in dominant model significantly increased HCC risk in women, compared to female healthy controls (AOR = 1.85, 95% CI = 1.20–2.84) or female HCC-free subjects (AOR = 1.62, 95% CI = 1.14–2.31). rs4938723 CC genotype and rs11614913 TC genotype were significantly associated with increased frequencies of the HCC-related HBV mutations T1674C/G and G1896A, respectively. rs11614913 was not significantly associated with HCC risk, but its CC genotype significantly enhanced the effect of rs4938723 in women. In multivariate regression analyses, rs4938723 in dominant model increased HCC risk (AOR = 1.62, 95% CI = 1.05–2.49), whereas its multiplicative interaction with C1730G, a HBV mutation inversely associated with HCC risk, reduced HCC risk (AOR = 0.34, 95% CI = 0.15–0.81); rs11614913 strengthened the G1896A effect but attenuated the A3120G/T effect on HCC risk. rs4938723 might be a genetic risk factor of HCC but its effect on HCC is significantly affected by the HBV mutations. rs11614913 might not be a HCC susceptible factor but it might affect the effects of the HBV mutations or rs4938723 on HCC risk.
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影响因子：
13.5
作者：
Hou, Weihong;Tian, Qing;Zheng, Jianyu;Bonkovsky, Herbert L.
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