HBV不同基因型致癌风险差异的系统综述和Meta分析

吴明山; 刘振球; 吴学福; 施婷婷; 张欣; 张铁军

doi:10.16462/j.cnki.zhjbkz.2021.03.014

HBV不同基因型致癌风险差异的系统综述和Meta分析

doi: 10.16462/j.cnki.zhjbkz.2021.03.014

200032 上海，复旦大学公共卫生学院流行病学教研室，公共卫生安全教育部重点实验室

基金项目:

国家自然科学基金 81772170

详细信息

通讯作者:
张铁军，E-mail: tjzhang@shmu.edu.cn

中图分类号: R735.7
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- 被引次数: 0
出版历程
- 收稿日期: 2020-09-14
- 修回日期: 2021-01-04
- 刊出日期: 2021-03-10

A systematic review and Meta-analysis on the carcinogenic risk difference of HBV subtypes

Department of Epidemiology, School of Public Health, Fudan University, China and Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai 200032, China

Funds:

National Natural Science Foundation of China 81772170

More Information

Corresponding author: ZHANG Tie-jun, E-mail: tjzhang@shmu.edu.cn

摘要

摘要: 目的探究不同基因型的HBV引发肝细胞癌(简称“肝癌”)风险差异及其潜在机制。方法通过检索数据库PubMed、Web of Science、Embase、中国知网(China national knowledge infrastructure, CNKI)及万方数据获取相关数据，利用Meta分析的方法进行数据整合。从National Center for Biotechnology Information(NCBI)Genbank数据库获取HBV的DNA序列，并分析不同基因型的HBV危险突变发生频率。结果共检出相关文献1 066篇，经筛检纳入符合要求文献17篇。总调查人数为16 288例，其中肝癌患者3 613例。Meta分析结果显示，感染HBV C基因型患者罹患肝癌风险较A、B及D基因型高，而感染A、B及D基因型的患者发生肝癌风险差异无统计学意义(均有P＞0.05)。HBV DNA突变频率分析结果显示，C基因型中危险突变发生频率高于其他基因型。结论 HBV C基因型与其他主要基因型相比，发生肝癌的风险更高，这可能归因于C基因型发生危险突变的频率更高。
- 乙型肝炎 /
- 基因型 /
- 肝细胞癌 /
- Meta分析
Abstract: Objective To explore the risk difference and potential mechanisms on the hepatocellular carcinogenesis of different HBV genotypes. Methods Literatures were retrieved from PubMed, Web of Science, Embase databases Wanfang data and CNKI. Data were synthesized by meta-analysis methods. HBV sequences were obtained from NCBI-GenBank and the mutation frequency of different HBV genotypes were calculated. Results A total of 1 066 studies were retrieved via literature search. Finally, 17 studies were included in the Meta-analysis after eligibility screening. The total number of study subjects was 16 288, including 3 613 liver cancer patients. Patients with HBV C genotype had a higher risk of liver cancer than genotypes A, B, and D. While no significant difference in the risk of liver cancer across genotypes A, B and D was observed. The frequency of mutations indicated that most mutations were more frequently occurred in genotype C compared with other genotypes. Conclusions HBV genotype C is associated with a higher risk of hepatocellular carcinoma than other genotypes, which might due to more risk mutations genotype C HBV possessed.
- HBV /
- Genotype /
- Liver cancer /
- Meta-analysis

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图 1 文献筛选流程

Figure 1. Literature selection and inclusion process flow

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图 2 不同基因型与肝癌发生相关性Meta分析森林图

注：A：C基因型vs.A基因型；B：C基因型vs.B基因型；C：C基因型vs.D基因型；D：A基因型vs.B基因型；E：A基因型vs.D基因型；F：B基因型vs.D基因型。

Figure 2. Forest plot of the association between different genotypes and the risk of hepatocellular carcinoma

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图 3 用剪补法绘制B基因型和C基因型发生肝癌风险差异的漏斗图

Figure 3. Filled funnel plots through trim-and-fill method on the difference of risk of liver cancer between genotype B and genotype C

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图 4 不同基因型位点突变频率

Figure 4. The frequency of mutations in different genotypes

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表 1 纳入文献基本情况

Table 1. Characteristic of included studies

作者及年份	地区	研究人数	肝癌人数	研究的基因型	研究设计	质量评分
杨家红2013^[9]	中国大陆	1 152	112	B、C	横断面研究	A-6
郑丹2015^[10]	中国大陆	123	53	B、C	病例对照研究	N-6
Chen 2012^[11]	中国大陆	466	156	B、C	病例对照研究	N-6
Kao 2000^[12]	中国台湾	270	80	A、B、C、D、	横断面研究	A-7
Fujie 2001^[13]	日本	109	58	B、C	病例对照研究	N-5
陈岳明2009^[14]	中国大陆	175	86	B、C	横断面研究	A-5
Asim 2010^[15]	印度	189	88	A、D	病例对照研究	N-7
Chen 2014^[16]	中国大陆	328	97	B、C	病例对照研究	N-7
Sumi 2003^[7]	日本	585	74	A、B、C	横断面研究	A-8
Sung 2008^[17]	中国香港	200	100	B、C	病例对照研究	N-6
Toan 2006^[18]	越南	375	84	A、B、C、D	横断面研究	A-8
Wen 2015^[19]	中国大陆	3 067	1 507	B、C、D	病例对照研究	N-7
Yang 2008^[6]	中国台湾	2 762	153	B、C	横断面研究	A-9
Yin 2008^[20]	中国大陆	1 121	462	A、B、C、D	横断面研究	A-7
Yu 2005^[21]	中国台湾	470	154	A、B、C	病例对照研究	N-7
Yuen 2004^[22]	中国香港	270	90	B、C	病例对照研究	N-6
Li 2010^[23]	中国大陆	4 300	203	B、C、D	病例对照研究	N-5
注：A：AHRQ，横断面文献质量评价工具；N：NOS，病例对照文献质量评价工具。

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表 2 亚组分析

Table 2. Subgroup analysis

分组	研究数量	样本量	OR(95% CI)值	I²值(%)	P值
研究类型
横断面研究	7	6 013	2.18(1.34~3.52)	84	0.002
病例对照研究	9	8 656	3.22(1.78~5.83)	92	< 0.001
地区
中国大陆	8	10 071	3.24(1.76~5.97)	94	< 0.001
其他	8	4 598	2.19(1.34~3.58)	82	0.002

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