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Int. J. Mol. Sci. 2016, 17(10), 1708; doi:10.3390/ijms17101708

Potential Susceptibility Mutations in C Gene for Hepatitis B-Related Hepatocellular Carcinoma Identified by a Two-Stage Study in Qidong, China

1
Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, China
2
Department of Infectious Disease, Affiliated Hospital of Nantong University, Nantong 226001, China
3
Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
4
Qidong Liver Cancer Institute, Qidong 226200, China
*
Author to whom correspondence should be addressed.
Academic Editors: Tatsuo Kanda and Stephen A. Bustin
Received: 12 May 2016 / Revised: 20 September 2016 / Accepted: 26 September 2016 / Published: 11 October 2016
(This article belongs to the Special Issue Hepatitis Virus Infection and Research)
View Full-Text   |   Download PDF [236 KB, uploaded 11 October 2016]

Abstract

A two stage study was conducted to explore new potential mutations in the full genome of hepatitis B virus (HBV) on the progression of hepatocellular carcinoma (HCC) in Qidong, China. In stage 1, full genomes of HBV were compared between 30 HCC cases and 30 controls. In stage 2, an independent case–control study including 100 HCC cases and 100 controls was enrolled to verify the relationship between hot-spot mutations and HCC development. Furthermore, a longitudinal study was conducted on 11 HCC cases with serial serum samples available before HCC diagnosis. A total of 10 mutations (including pre-S2 start codon mutation and pre-S deletion in pre-S gene, G1613A, C1653T, A1762T, and G1764A mutations in X gene, A2159G, A2189Y, G2203W, and C2288R mutations in C gene) showed an increased risk of HCC. In the validation study, pre-S deletion, C1653T, A1762T/G1764A, A2159G, A2189Y, G2203W, and C2288R mutations were associated with increased HCC risk in univariate analysis. Multivariate analysis indicated that pre-S deletion, A1762T/G1764A, A2159G, and A2189Y mutations were independently related with HCC development. Moreover, a significant biological gradient of HCC risk by number of mutations in the C gene was observed. Longitudinal observation demonstrated a gradual combination of the above mutations accumulated during the progression of HCC. View Full-Text
Keywords: hepatocellular carcinoma; mutation; C gene; hepatitis B virus hepatocellular carcinoma; mutation; C gene; hepatitis B virus
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. (CC BY 4.0).

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Qu, L.; Zhang, H.; Liu, J.; Liu, T.; Shen, X.; Chen, T.; Ni, Z.; Lu, C. Potential Susceptibility Mutations in C Gene for Hepatitis B-Related Hepatocellular Carcinoma Identified by a Two-Stage Study in Qidong, China. Int. J. Mol. Sci. 2016, 17, 1708.

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