A Functional Insertion/Deletion Polymorphism in the Proximal Promoter of CD3G Is Associated with Susceptibility for Hepatocellular Carcinoma in Chinese Population

Jiang, Lingling; Xu, Jingya; Ni, Jianqiang; Gao, Xueren; Zhu, Zhansheng; Dong, Dong; Wang, Xiaoshu; Shi, Chunhua; Tao, Xiaoyang; Dong, Wanli; Gao, Yuzhen
September 2012
DNA & Cell Biology;Sep2012, Vol. 31 Issue 9, p1480
Academic Journal
Hepatocellular carcinoma (HCC) represents the most common primary malignancy of the liver with a worldwide increasing incidence. Although the risk factors for HCC are well characterized, the molecular mechanisms responsible for malignant transformation of hepatocytes are not well understood. In this study, a case-control study including 291 HCC patients and 294 healthy controls was conducted to investigate the association between HCC susceptibility and with a 4-bp insertion/deletion polymorphism (rs66465034) in the proximal promoter of CD3G. Logistic regression analysis showed that the heterozygote and the homozygote 4-bp ins/ins confer a significantly increased risk of HCC after controlling for other covariates (adjusted odds ratio [OR]=1.51, 95% confidence interval [C.I.] 1.01-2.27, p=0.040; OR=1.71, 95% C.I. 1.07-2.89, p=0.025, respectively). Carriage of the 4-bp insertion allele was associated with a greatly increased risk of developing the disease (OR=1.30, 95% C.I. 1.02-1.64, p=0.027). Moreover, hepatitis B virus (HBV) stratification analysis showed that the differences between cases and controls were more obvious in HBV-positive than in the HBV-negative population, suggesting a possible role of this polymorphism in the immune regulation during HBV infection. Further, luciferase-based transient transfection assays revealed that rs66465034 can affect promoter activity of CD3G, indicating its possible functional significance. Our data suggested that common genetic polymorphisms in CD3G may influence HCC risk in Chinese population. Considering the relative small sample size, replication in other populations with larger sample size and further functional analysis are required for fully understanding the roles of CD3G polymorphisms in predisposition for HCC. Not only are viral infections associated with hepatocellular carcinoma, host gene polymorphisms may increase susceptibility. In this study, one of the signaling chains of the T cell receptor, the CD3γ, was shown to be a risk factor in Asians.


Related Articles

  • Association between indel polymorphism in the promoter region of lncRNA GAS5 and the risk of hepatocellular carcinoma. Ruiyang Tao; Shuxiang Hu; Shouyu Wang; Xianju Zhou; Qing Zhang; Chaoqun Wang; Xiankun Zhao; Wei Zhou; Suhua Zhang; Chengtao Li; Hua Zhao; Yan He; Shaohua Zhu; Jiejie Xu; Yizhou Jiang; Lijuan Li; Yuzhen Gao // Carcinogenesis;Oct2015, Vol. 36 Issue 10, p1136 

    The growth arrest special 5 (GAS5) is known to be involved in various cancers. However, its expression regulation remains unclear. Polymorphisms in the promoter region of GAS5 may affect its expression and be associated with cancer susceptibility. In this research, we first evaluated the...

  • Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Jiang, De-Ke; Sun, Jielin; Cao, Guangwen; Liu, Yao; Lin, Dongxin; Gao, Yu-Zhen; Ren, Wei-Hua; Long, Xi-Dai; Zhang, Hongxing; Ma, Xiao-Pin; Wang, Zhong; Jiang, Wei; Chen, Tao-Yang; Gao, Yong; Sun, Liang-Dan; Long, Ji-Rong; Huang, Hui-Xing; Wang, Dan; Yu, Hongjie; Zhang, Pengyin // Nature Genetics;Jan2013, Vol. 45 Issue 1, p72 

    To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6...

  • Association of IFN-γ gene polymorphism and levels in HBV related disease chronicity in India. Saxena, Roli; Chawla, Y. K.; Kaur, Jyotdeep // BMC Infectious Diseases;2012 Supplement, Vol. 12 Issue Supplment 1, p1 

    The article presents a study on the association of IFN-y gene polymorphism in the prevalence of hepatitis B virus (HBV) related diseases in India. The authors aim to determine the link between the levels of IFN-y polymorphism in hepatocellular carcinoma (HCC) cases in the country. They note that...

  • Associations of pri-miR-34b/c and pre-miR-196a2 Polymorphisms and Their Multiplicative Interactions with Hepatitis B Virus Mutations with Hepatocellular Carcinoma Risk. Han, Yifang; Pu, Rui; Han, Xue; Zhao, Jun; Zhang, Yuwei; Zhang, Qi; Yin, Jianhua; Xie, Jiaxin; Shen, Qiuxia; Deng, Yang; Ding, Yibo; Li, Weiping; Li, Juhong; Zhang, Hongwei; Cao, Guangwen // PLoS ONE;Mar2013, Vol. 8 Issue 3, p1 

    Background: 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...

  • Smoking, Hepatitis B Virus Infection, and Development of Hepatocellular Carcinoma. Sherman, Morris; Llovet, Josep M. // JNCI: Journal of the National Cancer Institute;Nov2011, Vol. 103 Issue 22, p1642 

    An introduction to the journal is presented in which the editor discusses two articles published within the issue on the risk factors for hepatocellular carcinoma including one on the incidence of hepatocellular carcinoma in Greenlanders with chronic Hepatitis B virus (HBV) infection, and...

  • XRCC1 Arg399Gln genetic polymorphism and the risk of hepatocellular carcinoma: a meta-analysis. Qi, Yunpeng; Cui, Lianhua; Song, Yang; Li, Na // Molecular Biology Reports;Feb2014, Vol. 41 Issue 2, p879 

    The X-ray repair cross-complementing group 1 (XRCC1) gene, one of over 20 genes that participate in the base excision repair pathway, is thought to account for differences in susceptibility to hepatocellular carcinoma. To assess the relationship between the XRCC1 Arg399Gln polymorphism and the...

  • rs3746444 Polymorphism and Susceptibility to Hepatocellular Carcinoma: Evidence from Published Studies. Liu, Fangfeng; Lin, Hongfeng; Cheng, Ying; Yang, Lei; Liu, Yongfeng // Cell Biochemistry & Biophysics;Dec2014, Vol. 70 Issue 3, p1957 

    The present study was undertaken to quantitatively evaluate the association between rs3746444 polymorphism and HCC risk. In this analysis with 667 cancer cases and 1,006 control subjects, we summarized 4 eligible case-control studies by searching databases of PubMed, EMBASE, and CNKI. The...

  • Association of p53 codon 72 polymorphism with susceptibility to hepatocellular carcinoma in a Chinese population from northeast Sichuan. JIAJING CAI; YAN CAI; QIANG MA; FAN CHANG; LEI XU; GUOYUAN ZHANG; XIAOLAN GUO // Biomedical Reports;Feb2017, Vol. 6 Issue 2, p217 

    The p53 tumor suppressor gene is key in tumor development and progression, and the single nucleotide polymorphism (SNP) of the p53 gene codon 72 (p53Arg/Pro) changes the structure of the protein. In addition, it affects its activity, which may affect cancer risk. The aim of the present study was...

  • The IL-8 Gene Polymorphisms and the Risk of the Hepatitis B Virus/Infected Patients. Qin, Xue; Deng, Yan; Liao, Xiang-Cheng; Mo, Cui-Ju; Li, Xi; Wu, Hui-Ling; He, Ya-Ni; Huang, Xia-Mei; Peng, Tao; Chen, Zhi-Ping; Li, Shan // DNA & Cell Biology;Jun2012, Vol. 31 Issue 6, p1125 

    Interleukin-8 ( IL-8) belongs to the superfamily of CXC chemokines, contributing to human cancer progression through potential mitogenic, angiogenic, and motogenic functions. We hypothesize that the functional polymorphism of IL-8 may influence the inflammatory process during pathological stage...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics