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International Journal of Endocrinology
Volume 2015 (2015), Article ID 854530, 9 pages
http://dx.doi.org/10.1155/2015/854530
Review Article

Role of Sex Hormones in the Development and Progression of Hepatitis B Virus-Associated Hepatocellular Carcinoma

1Epidemiology Unit, National Cancer Institute of Naples “G. Pascale Foundation”, IRCCS, 80131 Naples, Italy
2Department of Onco-Hematology, IRCCS, Cancer Referral Center of Basilicata, 85028 Rionero in Vulture, Italy
3Department of Medicine and Surgery, University of Salerno, 84081 Fisciano, Italy
4Animal Facility, National Cancer Institute of Naples “G. Pascale Foundation”, IRCCS, 80131 Naples, Italy
5Department of Pharmacy, University of Salerno, 84084 Fisciano, Salerno, Italy
6Department of Surgery, National Cancer Institute of Naples “G. Pascale Foundation”, IRCCS, 80131 Naples, Italy
7Department of Experimental Medicine, II University of Naples, 81055 Naples, Italy
8National Cancer Institute “G. Pascale Foundation”, IRCCS, 80131 Naples, Italy

Received 12 May 2015; Revised 29 June 2015; Accepted 1 July 2015

Academic Editor: Haifei Shi

Copyright © 2015 Maurizio Montella et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Infection with hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC) in developed countries. Epidemiological reports indicate that the incidence of HBV-related HCC is higher in males and postmenopausal females than other females. Increasing evidence suggests that sex hormones such as androgens and estrogens play an important role in the progression of an HBV infection and in the development of HBV-related HCC. While androgen is supposed to stimulate the androgen signaling pathway and cooperate to the increased transcription and replication of HBV genes, estrogen may play a protecting role against the progression of HBV infections and in the development of HBV-related HCC through decreasing HBV RNA transcription and inflammatory cytokines levels. Additionally, sex hormones can also affect HBV-related hepatocarcinogenesis by inducing epigenetic changes such as the regulation of mRNA levels by microRNAs (miRNAs), DNA methylation, and histone modification in liver tissue. This review describes the molecular mechanisms underlying the gender disparity in HBV-related HCC with the aim of improving the understanding of key factors underneath the sex disparity often observed in HBV infections. Furthermore, the review will propose more effective prevention strategies and treatments of HBV-derived diseases.