Polymorphisms in the precursor microRNAs and aflatoxin B1-related hepatocellular carcinoma
Polymorphisms in the precursor microRNAs and aflatoxin B1-related hepatocellular carcinoma
复制标题
前体 MicroRNA 和黄曲霉毒素 B1 相关肝细胞癌中的多态性
DOI：
10.1002/mc.22350
复制
发表时间：
2016-06-01
影响因子：
4.6
通讯作者：
Xia, Qiang
中科院分区：
文献类型：
--
作者：
Long, Xi-Dai;Huang, Xiao-Ying;Xia, Qiang
在肝细胞癌（HCC）中观察到一些microRNA（miRNAs）的表达改变;然而，尚未研究黄曲霉毒素B1（AFB 1）相关HCC中前体miRNAs（pre-miRNAs）的遗传多态性。在中国高AFB 1暴露地区进行了一项基于医院的病例对照研究，包括1，706例HCC病例和2，270例对照，无任何肝脏疾病或肿瘤，以评估前体miRNA中的48个多态性与AFB 1相关HCC风险和预后之间的关系。在48个多态性中，只有rs 28599926（在miRNA 1268 a中）影响HCC风险。与rs 28599926 C等位基因纯合子（rs 28599926-CC）相比，rs 28599926 T等位基因型（rs 28599926-CT或-TT）增加HCC风险（比值比[OR]分别为1.63和5.52，95%可信区间[CI]分别为1.40-1.90和4.27-7.14）。在联合效应分析中还观察到风险基因型和AFB 1暴露状态之间的显著交互效应。该多态性不仅与肿瘤体积增大、门静脉癌风险增高、肿瘤去分化有关，而且与AFB 1加合物水平增高、TP 53基因突变风险增高有关。此外，rs 28599926改变了病例的肿瘤无复发生存期（风险比[HR]：2.86，95% CI：2.36-3.43）和总生存期（HR：2.12，95% CI：1.86-2.41）。此外，miR-1268 a的一个靶点是ADAMTS 4 mRNA，rs 28599926多态性可能会改变ADAMTS 4的表达。这些发现表明，前体miRNA的多态性可能是AFB 1相关HCC的风险和预后生物标志物，miR-1268 a中的rs 28599926是这样一个潜在的候选者。(c)2015 Wiley Periodicals，Inc.
The altered expression of some microRNAs (miRNAs) is observed in hepatocellular carcinoma (HCC); however, the genetic polymorphisms in the precursor miRNAs (pre-miRNAs) in aflatoxin B1 (AFB1)-related HCC have not yet been investigated. A hospital-based case-control study, including 1,706 HCC cases and 2,270 controls without any liver diseases or tumors, was conducted in a high AFB1 exposure area of China to assess the relationship between 48 polymorphisms in the pre-miRNAs and AFB1-related HCC risk and prognosis. Among 48 polymorphisms, only rs28599926 (in the miRNA 1268a) affected HCC risk. Compared with the homozygote of rs28599926C alleles (rs28599926-CC), the genotypes of rs28599926 T alleles (namely rs28599926-CT or -TT) increased HCC risk (odds ratio [OR]: 1.63 and 5.52, 95% confidence interval [CI]: 1.40-1.90 and 4.27-7.14, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. This polymorphism was associated not only with larger tumor size, higher portal vein tumor risk, and tumor dedifferentiation, but also with higher AFB1 adducts levels and increasing the mutation risk of TP53 gene. Furthermore, rs28599926 modified the tumor recurrence-free survival (hazard ratio [HR]: 2.86, 95% CI: 2.36-3.43) and overall survival (HR: 2.12, 95% CI: 1.86-2.41) of cases. Additionally, one target of miR-1268a was show to be the ADAMTS4 mRNA and rs28599926 polymorphism might modify ADAMTS4 expression. These findings indicate that polymorphisms in the pre-miRNAs may be risk and prognostic biomarkers of AFB1-related HCC, and rs28599926 in miR-1268a is such a potential candidate. (c) 2015 Wiley Periodicals, Inc.