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Gender disparity in hepatocellular carcinoma (HCC): multiple underlying mechanisms

Science China Life Sciences volume 60, pages 575–584 (2017)Cite this article

Abstract

On the global scale, hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) especially in regions of Asia where HBV infection is endemic. Epidemiological studies show that the incidence of inflammation-driven HCC in males is three times as high as in females. Recent studies suggest that sex hormones have a crucial role in the pathogenesis and development of HBV-induced HCC. We found that the estrogen/androgen signaling pathway is associated with decreased/increased transcription and replication of HBV genes and can promote the development of HBV infections by up/downregulating HBV RNA transcription and inflammatory cytokines levels, which in turn slow down the progression of HBV-induced HCC. Additionally, sex hormones can also affect HBV-related HCC by inducing epigenetic changes. The evidence that both morphology and function of the human liver are affected by sex hormones was found over 60 years ago. However, the underlying molecular mechanism largely remains to be elucidated. This review focuses mainly on the molecular mechanisms behind the sex difference in HCC associated with HBV and other factors. In addition, several potential treatment and therapeutic strategies for inflammation-driven HCC will be introduced in this review.

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Acknowledgements

This work was supported by the State Key Project for Liver Cancer (2012ZX10002009), National Natural Science Foundation of China (81301811, 81521091, 81422032, 81272212, 81672860, 81372674, and 91529303), Science Foundation of Shanghai (134119a3700), and Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12010201).

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  1. Contributed equally to this work

Affiliations

  1. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University, Shanghai, 200438, China

    Bo Zheng, Yan-Jing Zhu, Hong-Yang Wang & Lei Chen

  2. National Center for Liver Cancer, Shanghai, 201805, China

    Bo Zheng, Yan-Jing Zhu, Hong-Yang Wang & Lei Chen

  3. State Key Laboratory of Oncogenes and related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Hong-Yang Wang

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  1. Bo Zheng
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  2. Yan-Jing Zhu
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  3. Hong-Yang Wang
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  4. Lei Chen
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Correspondence to Hong-Yang Wang or Lei Chen.

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Zheng, B., Zhu, YJ., Wang, HY. et al. Gender disparity in hepatocellular carcinoma (HCC): multiple underlying mechanisms. Sci. China Life Sci. 60, 575–584 (2017). https://doi.org/10.1007/s11427-016-9043-9

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  • DOI: https://doi.org/10.1007/s11427-016-9043-9

Keywords

  • gender disparity
  • hepatocarcinoma
  • heptitis B virus