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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 8, 2016; 8(10): 485-498
Published online Apr 8, 2016. doi: 10.4254/wjh.v8.i10.485
Host nucleotide polymorphism in hepatitis B virus-associated hepatocellular carcinoma
Shilu Mathew, Hany Abdel-Hafiz, Abbas Raza, Kaneez Fatima, Ishtiaq Qadri
Shilu Mathew, Center of Excellence in Genomic Medicine Research, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
Hany Abdel-Hafiz, University of Colorado Denver AMC, Aurora, CO 80045, United States
Abbas Raza, Department of Immunobiology, University of Vermont, Burlington, VT 05405, United States
Kaneez Fatima, IQ-Institute of Infection and Immunity, Lahore 54000, Pakistan
Ishtiaq Qadri, King Fahd Medical Research Center, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
Author contributions: All authors contributed to this manuscript.
Supported by The STACK-Large grant 162-34 to Ishtiaq Qadri; IQ Foundation.
Conflict-of-interest statement: All authors disclose no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ishtiaq Qadri, PhD, Professor, King Fahd Medical Research Center, King Abdul Aziz University, PO Box 80216 Jeddah 21589, Saudi Arabia. ishtiaq80262@yahoo.com
Telephone: +966-12-6400000 Fax: +966-12-6952067
Received: September 12, 2015
Peer-review started: September 15, 2015
First decision: November 13, 2015
Revised: December 4, 2015
Accepted: March 7, 2016
Article in press: March 9, 2016
Published online: April 8, 2016
Processing time: 199 Days and 22.7 Hours
Abstract

Hepatocellular carcinoma (HCC) is etiologically linked with hepatitis B virus (HBV) and is the leading cause of death amongst 80% of HBV patients. Among HBV affected patients, genetic factors are also involved in modifying the risk factors of HCC. However, the genetic factors that regulate progression to HCC still remain to be determined. In this review, we discuss several single nucleotide polymorphisms (SNPs) which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection such as cyclooxygenase (COX)-2 expression specifically at COX-2 -1195G/A in Chinese, Turkish and Egyptian populations, tumor necrosis factor α and the three most commonly studied SNPs: PAT-/+, Lys939Gln (A33512C, rs2228001) and Ala499Val (C21151T, rs2228000). In genome-wide association studies, strong associations have also been found at loci 1p36.22, 11q22.3, 6p21 (rs1419881, rs3997872, rs7453920 and rs7768538), 8p12 (rs2275959 and rs37821974) and 22q11.21. The genes implicated in these studies include HLA-DQB2, HLA-DQA1, TCF19, HLA-C, UBE2L3, LTL, FDX1, MICA, UBE4B and PG. The SNPs found to be associated with the above-mentioned genes still require validation in association studies in order to be considered good prognostic candidates for HCC. Screening of these polymorphisms is very beneficial in clinical experiments to stratify the higher or lower risk for HCC and may help in designing effective and efficient HCC surveillance programs for chronic HBV-infected patients if further genetic vulnerabilities are detected.

Keywords: Hepatitis B virus; Hepatocellular carcinoma; Subtypes; Genetic polymorphism; Liver cirrhosis

Core tip: In this review, we discuss various common associations between hepatitis B virus (HBV) and host polymorphisms. These single nucleotide polymorphisms which have been found to be associated with various genes still require validation in association studies in order to be considered good prognostic candidates for hepatocellular carcinoma (HCC). Screening of these polymorphisms is very beneficial in clinical experiments to stratify the higher or lower risk for HCC and may help in designing effective and efficient HCC surveillance programs for chronic HBV-infected patients if further genetic vulnerabilities are detected.