Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China; Digestive Endoscopy Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China.
Mol Carcinog. 2013 Nov;52 Suppl 1:E148-54. doi: 10.1002/mc.22062. Epub 2013 Jul 19.
Genetic variations in miRNA processing genes may affect the biogenesis of miRNA, hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In the present study, we hypothesized that potentially functional polymorphisms in 3'-untranslated region (UTR) of miRNA processing genes might contribute to susceptibility of HBV infection and HCC development. To test the hypothesis, we genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were associated with a significant decreased risk of HCC (adjusted OR = 0.79, 95% CI = 0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes increased the risk of HBV persistent infection compared with AA genotype (adjusted OR = 1.35, 95% CI = 1.03-1.77). However, PIWIL1 rs10773771 CT/CC variant genotypes were associated with an approaching decreased risk of HCC (adjusted OR = 0.86, 95% CI = 0.73-1.01) and similar with RAN rs3803012 AG/GG (adjusted OR = 0.80, 95% CI = 0.61-1.06). Furthermore, reporter gene assays indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change the binding ability of miRNAs to the 3'UTR of the three genes (DICER1, RAN, and PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC.
miRNA 加工基因中的遗传变异可能会影响 miRNA 的生物发生，从而影响乙型肝炎病毒（HBV）感染和肝细胞癌（HCC）的发展。在本研究中，我们假设 miRNA 加工基因 3'UTR 中的潜在功能多态性可能导致 HBV 感染和 HCC 发展的易感性。为了验证这一假设，我们对 1300 例 HBV 阳性 HCC 癌症病例、1344 例 HBV 持续携带者和 1344 例 HBV 自然清除受试者进行了病例对照研究，对三个选定的 SNP（DICER1 中的 rs1057035、RAN 中的 rs3803012 和 PIWIL1 中的 rs10773771）进行了基因分型。我们观察到，与野生型 TT 相比，DICER1 rs1057035 CT/CC 变体基因型与 HCC 的显著降低风险相关（调整后的 OR = 0.79，95%CI = 0.64-0.96），而 RAN rs3803012 AG/GG 变体基因型增加了 HBV 持续感染的风险，与 AA 基因型相比（调整后的 OR = 1.35，95%CI = 1.03-1.77）。然而，PIWIL1 rs10773771 CT/CC 变体基因型与 HCC 的降低风险相关（调整后的 OR = 0.86，95%CI = 0.73-1.01），与 RAN rs3803012 AG/GG 相似（调整后的 OR = 0.80，95%CI = 0.61-1.06）。此外，报告基因检测表明，这三个 SNP（rs1057035、rs3803012 和 rs10773771）可能分别改变 miRNA 与三个基因（DICER1、RAN 和 PIWIL1）3'UTR 的结合能力。这些发现表明，DICER1 rs1057035、RAN rs3803012 和 PIWIL1 rs10773771 可能导致与 HBV 相关的 HCC 风险增加。
