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miRNA196a-2和miRNA146a单核苷酸多态性与中国人群肝细胞癌易感性的关联

Association between single nucleotide polymorphisms in miRNA196a-2 and miRNA146a and susceptibility to hepatocellular carcinoma in a Chinese population.

作者信息

Zhang Jun, Wang Rui, Ma Yan-Yun, Chen Lin-Qi, Jin Bo-Han, Yu Hua, Wang Jiu-Cun, Gao Chun-Fang, Liu Jie

机构信息

Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2013;14(11):6427-31. doi: 10.7314/apjcp.2013.14.11.6427.

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world and deeply threatens people's health, especially in China. Techniques of early diagnosis, prevention and prediction are still being discovered, among which the approaches based on single nucleotide polymorphisms in microRNA genes (miRNA SNPs) are newly proposed and show prospective potential. In particular, the association between SNPs in miRNA196a-2 (rs11614913) and miRNA146a (rs2910164) and HCC has been investigated. However, the conclusions made were conflicting, possibly due to insufficient sample size or population stratification. Further confirmations in well-designed large samples are still required. In this study, we verified the association between these two SNPs and the susceptibility to HCC by MassARRAY assay in a 2,000 large Chinese case-control sample. Significant association between rs11614913 and HCC was confirmed. Subjects with the genotype of CT+TT or T allele in rs11614913 were more resistant to HCC (CT+TT: OR (95% CI)=0.73 (0.57-0.92), P=0.01; T allele: OR (95% CI)=0.85 (0.75-0.97), P=0.02) and HBV-related HCC (CT+TT: OR (95% CI)=0.69 (0.53-0.90), P=0.01; T allele: OR (95% CI)=0.82 (0.71-0.95), P=0.01). The affected carriers of CT or TT also tended to have lower levels of serum AFP (P=0.01). This study demonstrated a role of rs11614913 in the etiology of HCC. Further research should focus on the clinical use of this miRNA SNP, so as to facilitate conquering HCC.

摘要

肝细胞癌(HCC)是世界上最常见的癌症之一,严重威胁着人们的健康,在中国尤为如此。早期诊断、预防和预测技术仍在不断探索中,其中基于微小RNA基因(miRNA)单核苷酸多态性(SNP)的方法是新提出的,且显示出潜在的前景。特别是,已经对miRNA196a - 2(rs11614913)和miRNA146a(rs2910164)中的SNP与HCC之间的关联进行了研究。然而,得出的结论相互矛盾,这可能是由于样本量不足或人群分层所致。仍需要在设计良好的大样本中进行进一步验证。在本研究中,我们通过MassARRAY分析在2000例中国大型病例对照样本中验证了这两个SNP与HCC易感性之间的关联。证实了rs11614913与HCC之间存在显著关联。rs11614913基因型为CT + TT或携带T等位基因的受试者对HCC的抵抗力更强(CT + TT:OR(95%CI)=0.73(0.57 - 0.92),P = 0.01;T等位基因:OR(95%CI)=0.85(0.75 - 0.97),P = 0.02)以及对HBV相关HCC的抵抗力更强(CT + TT:OR(95%CI)=0.69(0.53 - 0.90),P = 0.01;T等位基因:OR(95%CI)=0.82(0.71 - 0.95),P = 0.01)。CT或TT的受影响携带者血清AFP水平也往往较低(P = 0.01)。本研究证明了rs11614913在HCC病因学中的作用。进一步的研究应聚焦于这种miRNA SNP的临床应用,以便于攻克HCC。

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