Quantitative assessment of mutations in hepatitis B virus genome with liver cirrhosis and hepatocellular carcinoma development
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Lei Yu1,2,*, Bao-fang Zhang3,*, Ming-liang Cheng2, Xue-ke Zhao2, Quan Zhang2, Ya-xin Hu2, Hua-juan Liu2, Mao Mu2, Bi Wang2,4, Guo-zhen Yang2, Li-li Zhu2, Shuai Zhang5, Yu-mei Yao2, Yi-ju Cheng2, Wang-sheng Li6
1The First Affiliated Hospital of Jinan University, Guangdong 510632, Guangzhou, China
2The Affiliated Hospital, Guizhou Medical University, Guiyang 550004, Guizhou, China
3The First Affiliated Hospital, Soochow University, Suzhou 215006, Jiangsu, China
4Department of Eugenics and Genetics, Guiyang Maternal and Child Health-Care Hospital, Guiyang 550003, Guizhou, China
5Department of Interventional Radiology, Cancer Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China
6Department of Clinical Laboratory, Liupanshui People’s Hospital, Liupanshui 553401, Guizhou, China
*These authors contributed equally to this work and should be considered as co-first authors
Ming-liang Cheng, e-mail: email@example.com
Guo-zhen Yang, e-mail: firstname.lastname@example.org
Keywords: hepatitis B virus, hepatocellular carcinoma, liver cirrhosis, mutation, risk
Received: February 29, 2016 Accepted: April 28, 2016 Published: May 17, 2016
The long-term outcomes of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection are associated with specific HBV genotypes and mutations in the virus genome. However, a number of gene-disease association studies have yielded inconsistent results in the field. To investigate this inconsistency, we conducted a meta-analysis from 118 studies involving a total of 9,418 HCC cases, 2,697 LC cases, and 18,785 HBV-infected participants for 11 mutations of HBV to evaluate the epidemiological evidence of the relationship. Overall, 10 mutants (Pre-S mutation, A1762T/G1764A double mutations, G1896A, G1899A, T1753V, C1653T, G1766A, A1762T, G1764A, T1768A) were significantly associated with increased HCC risk with odds ratio (OR) range from 1.80 to 4.27, while no associations were found for C1858T. We found a significant dose–risk relationship between the number of mutations in HBV genome and HCC, in which high risks for HCC were associated with mutation numbers more than 5 (OR = 18.45, 95% CI: 7.86–43.29). By pooling 15 prospective studies, A1762T/G1764A, Pre-S, T1753V, and C1653T mutation was identified as good predictor of HCC risk, showing ORs from 1.73 to 4.54. In addition, significantly elevated LC risks were associated with 6 mutants (A1762T/G1764A double mutations, G1896A, G1899A, T1753V, C1653T, Pre-S mutation), with OR range from 1.76 to 4.10. Our results suggested that HBV mutations alone or in combination may be of clinical significance for predicting hepatocarcinogenesis.
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