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, Dong; Gao, Yu Zhen; Ren, Wei; Long, Xi; Zhang, Hongxing; Peng, Xiao; Wang, Zhong; Jiang, Wei; Chen, Tao Yang; Gao, Yong; Sun, Liang; Long, Ji Rong; Huang, Haoran; Wang, Dan; Yu, Hongjie; Zhang, Pengyin; Tang, Li; Peng, Bo; Cai, Hao; Liu, Ting Ting; Zhou, Ping; Liu, Fang; Lin, Xiaoling; Tao, Sha; Wan, Bo; Sai-Yin, He Xi Ge; Qin, Lun Xiu; Yin, Jianhua; Liu, Li; Wu, Chen; Pei, Yan; Zhou, Yuan; Zhai, Yun; Lu, Pei Xin; Tan, Aihua; Zuo, Xian Bo; Fan, Jia; Chang, Jiang; Gu, Xiaoli; Wang, Neng Jin; Li, Yang; Liu, Yin Kun; Zhai, Kan; Zhang, Hongwei; Hu, Zhibin; Liu, Jun; Yi, Qing; Xiang, Yong‐Bing; Shi, Rong; Ding, Qiang; Wang, Zheng; Shu, Xiao Ou; Mo, Zengnan; Shugart, Yin Yao; Zhang, Xue Jun; Zhou, Gangqiao; Shen, Hongbing; Zheng, S. Lilly; Xu, Jianfeng; Liu, Yu

doi:10.1038/ng.2483

Cited by 264 publications

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“…As described above, the HLA-II genetic polymorphisms are statistically associated with the outcomes of exposureto HBV [18][19][20][21][22][23][24][25][26][27] . This genetic background may predispose immune imbalance upon HBV infection.…”

Section: Interaction Of Genetic Predispositions Of Immune or Inflammamentioning

confidence: 99%

“…Genome-wide association study in the eastern Asian populations have shown that a total of 11 single nucleotide polymorphisms (SNPs) in genetic loci including HLA-DPA1 and HLA-DPB1, some SNPs in genetic loci including HLA-DQ and -DR, and a locus near HLA-Care significantly associated with CHB [18][19][20][21][22] . Interestingly, these SNPs in the loci encoding human leukocyte antigen-class II (HLA-II) are also significantly associated with vaccine response as well as the risks of acute-on-chronic liver failure, HBVrelated liver cirrhosis, and HBV-associated HCC [23][24][25][26][27] . Interestingly, different human races have different allelic frequencies of SNPs that affect the expression of HLA-DP, HLA-DQ, and the inhibitory component of NF-κB complex IκBa gene NFKBIA.…”

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confidence: 99%

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Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

Cao¹

2017

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How to cite this article: Cao GW. Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis. Hepatoma Res 2017;3:241-59.Non-resolving inflammation, which may be maintained by infection, pollution, and metabolic stimulants and their interactions with immunogenetic predisposition, provides a fertile field for cancer development. This is strongly evident in hepatocellular carcinoma. Here, the framework of a hypothesis called Cancer Evo-Dev is presented, based on the advances in hepatitis B virusinduced hepatocarcinogenesis. Several aspects central to this theory are as follows: (1) immune imbalance caused by the interaction of immunogenetic predispositions and hepatitis B virus infection maintains non-resolving inflammation; (2) active inflammation executants promote mutations in viral and host genomes via disbalancing mutagenic forces including cytidine deaminases and mutation-repairing forces including uracil-DNA glycosylases, thus promoting cancer-related somatic mutations and viral mutations; (3) a small percentage of the cells whose somatic mutations alter the survival signalling adapt to the inflammatory microenvironment, de-differentiate via demethylating role of cytidine deaminases, and reversely develop into tumor-initiating cells (TICs); (4) under the cultivation of some factors like POSTN from tumorinfiltrating fibroblasts and M2 macrophages, TICs acquire the stemness, cancer-stem cells obtain distinct metastatic and drug-resistant potentials under the selection pressure from distinct microenvironments; (5) glycolysis persistence in the presence of oxygen provides essential energy for cell survival and the raw material for DNA synthesis. Thus, cancer development is characterized by an evolutionary process of "mutation-selection-adaptation". The framework of Cancer Evo-Dev can be verified in other cancers. Cancer Evo-Dev lays theoretical foundation for understanding the mechanisms by which inflammation promotes cancer development, and it also plays a role in specific prophylaxis, prediction, and targeted treatment of cancers. Key words:Inflammation, hepatitis B virus, mutations, hepatoma, Cancer Evo-Dev ABSTRACTArticle history:

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Section: Interaction Of Genetic Predispositions Of Immune or Inflammamentioning

confidence: 99%

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confidence: 99%

Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

Cao¹

2017

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“…Genetic host factors are known to drive this association, with the identification of single nucleotide polymorphisms (SNPs). SNPs have been identified through genome wide association studies (GWAS): STAT4 (19), TPTE2 (20), CTLA-4 (21) and DCL1 (22) genes, as well as in the region containing the UBEB4, KIF1B and PGD genes (23). Additional SNPs have been described, but it is accepted that these identified SNPs only partially account for the variability in HCC susceptibility.…”

Section: Risk Factorsmentioning

confidence: 99%

Viral hepatitis and hepatocellular carcinoma: etiology and management

Zamor

deLemos

Russo

2017

J. Gastrointest. Oncol.

121

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Hepatitis B virus (HBV) risk and hepatocellular carcinoma (HCC) EpidemiologyIt is estimated that over 50% of HCC cases worldwide are related to chronic HBV (1,2). Since the implementation of worldwide HBV vaccination there has been an overall decline in the burden of HBV, yet the HBV burden remains quite high in various parts of the world. There are approximately 350-400 million people across the world infected with HBV, the majority reside in or originate from Asia. Each year HBV accounts for 749,000 new cases of HCC and 692,000 HCC-related deaths (3). The annual incidence of HCC is estimated to be <1% for non-cirrhotic HBV infected patients and 2-3% for those with cirrhosis. Because of worldwide and geographic variations in HBV incidence, the burden of HBV related HCC also varies. Asian-Pacific and sub-Saharan Africa represent the highest incidence of HCC worldwide. Much lower risk of HBV associated HCC is seen in the United States with less than 20% incidence. Due to its diversity, Europe has different areas: low risk (18%) in West and North and high risk (51%) East and South (4). Occult HBV or subclinical infection as defined by detectable HBV DNA in the liver but hepatitis B surface antigen (HBsAg) seronegativity is now recognized as increased risk for HCC. The risk is most notable in those over the age of 50 (5,6). Recently published data reveal that in China, the age-standardized death due to HBV-related HCC and cirrhosis in 2013 was 10.95 and 4.91 per 100,000 people (7). Fifty-five percent of all HCC cases worldwide are reported from China (8).In 1991, the WHO recommended the integration of the HBV vaccine into national immunization programs in countries with an HBV carrier prevalence of 8% or higher by 1995 and in all other countries by 1997 (9). The universal infant vaccination rate in sub-Saharan Africa was initially quite low at 5% in 2000 but increased to 72% by 2012. Parts of the Pacific region had the lowest immunization rates, but by 2012 had increased to the highest rates at 91%. Taiwan has an exceptionally higher This review outlines the various mechanisms and pathophysiology that contributes to this process. There will also be a review on the recommended screening for HCC. Treatment considerations, which are different for these viruses, will be outlined in this review.

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“…[67][68][69][70][71] These designs are hard to distinguish driver mutations from passenger mutations because cross-sectional case-control studies can only indicate statistical associations between factors of interest with the diseases. If loss-of-function or gain-of-function mutations can promote carcinogenesis, these mutations are more likely to be driver mutations.…”

Section: -55mentioning

confidence: 99%

Sleeping Beautytransposon system for genetic etiological research and gene therapy of cancers

Hou¹,

Deng³

et al. 2014

Cancer Biology & Therapy

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Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus–related hepatocellular carcinoma

Cited by 264 publications

References 44 publications

Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

Cancer Evo-Dev, a novel hypothesis derived from studies on hepatitis B virus-induced carcinogenesis

Viral hepatitis and hepatocellular carcinoma: etiology and management

Sleeping Beautytransposon system for genetic etiological research and gene therapy of cancers

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