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长链非编码RNA ZNRD1-AS1中的表达数量性状位点影响宫颈癌的发展。

Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence cervical cancer development.

作者信息

Guo Lanwei, Wen Juan, Han Jing, Jiang Jie, Xie Shuanghua, Feng Xiaoshuang, Wei Baojun, Dai Juncheng, Zhang Kai, Qi Jun, Ma Hongxia, Shi Jufang, Ren Jiansong, Zhang Yue, Dai Min, Hu Zhibin, Li Ni

机构信息

National Office for Cancer Prevention and Control, Cancer Institute and Hospital, Chinese Academy of Medical Sciences Beijing, China ; Department of Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital Zhengzhou, China.

Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University Nanjing, China.

出版信息

Am J Cancer Res. 2015 Jun 15;5(7):2301-7. eCollection 2015.

Abstract

Zinc ribbon domain containing 1 (ZNRD1) may play integral roles in immune response against HPV infection and cervical cancer. Its antisense transcript, ZNRD1-AS1, is an important regulator of ZNRD1. By bioinformatics analyses, we identified that several single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 may be expression quantitative trait loci (eQTLs) for ZNRD1. So we hypothesized that these eQTLs SNPs in ZNRD1-AS1 may influence the susceptibility of cervical cancer through influencing ZNRD1 expression. We designed a population-based case-control study containing 1486 cervical cancer patients and 1536 controls to test the associations of three ZNRD1 eQTLs SNPs (rs3757328, rs6940552 and rs9261204) in ZNRD1-AS1 with the risk of cervical cancer. Logistic regression analyses in additive genetic model showed that all the three eQTLs SNPs decreased the risk of cervical cancer. Compared with those carrying "0" variant allele, subjects carrying "1-6" variant alleles had a 20% decreased risk of cervical cancer. Moreover, the haplotype containing variant alleles of these three SNPs significantly decreased the risk of cervical cancer when compared with the most frequent haplotype. In conclusion, ZNRD1 eQTLs SNPs in ZNRD1-AS1 could have a predisposition for the development of cervical cancer.

摘要

含锌带结构域蛋白1(ZNRD1)可能在针对人乳头瘤病毒(HPV)感染和宫颈癌的免疫反应中发挥重要作用。其反义转录本ZNRD1-AS1是ZNRD1的重要调节因子。通过生物信息学分析,我们发现ZNRD1-AS1中的几个单核苷酸多态性(SNP)可能是ZNRD1的表达数量性状位点(eQTL)。因此,我们推测ZNRD1-AS1中的这些eQTL SNP可能通过影响ZNRD1的表达来影响宫颈癌的易感性。我们设计了一项基于人群的病例对照研究,纳入1486例宫颈癌患者和1536例对照,以检验ZNRD1-AS1中三个ZNRD1 eQTL SNP(rs3757328、rs6940552和rs9261204)与宫颈癌风险的关联。在加性遗传模型中的逻辑回归分析表明,所有这三个eQTL SNP均降低了宫颈癌风险。与携带“0”个变异等位基因的受试者相比,携带“1-6”个变异等位基因的受试者患宫颈癌的风险降低了20%。此外,与最常见单倍型相比,包含这三个SNP变异等位基因的单倍型显著降低了宫颈癌风险。总之,ZNRD1-AS1中的ZNRD1 eQTL SNP可能对宫颈癌的发生具有易感性。

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