Role of Sex Hormones in the Development and Progression of Hepatitis B Virus-Associated Hepatocellular Carcinoma.
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.
Epidemiology Unit, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.
Maurizio
M
Montella
Department of Onco-Hematology, IRCCS, Cancer Referral Center of Basilicata, 85028 Rionero in Vulture, Italy.
Giovanni
G
D'Arena
Epidemiology Unit, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.
Anna
A
Crispo
Department of Medicine and Surgery, University of Salerno, 84081 Fisciano, Italy.
Mario
M
Capunzo
Epidemiology Unit, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.
Flavia
F
Nocerino
Epidemiology Unit, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.
Maria
M
Grimaldi
Animal Facility, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.
Antonio
A
Barbieri
Department of Pharmacy, University of Salerno, 84084 Fisciano, Salerno, Italy.
Anna Maria
AM
D'Ursi
Department of Pharmacy, University of Salerno, 84084 Fisciano, Salerno, Italy.
Mario Felice
MF
Tecce
Department of Surgery, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.
Alfonso
A
Amore
Department of Experimental Medicine, II University of Naples, 81055 Naples, Italy.
Massimiliano
M
Galdiero
National Cancer Institute "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.
Gennaro
G
Ciliberto
Epidemiology Unit, National Cancer Institute of Naples "G. Pascale Foundation", IRCCS, 80131 Naples, Italy.
Aldo
A
Giudice