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Polymorphisms of Tumor Necrosis Factor-Alpha and Hepatocellular Carcinoma Risk: A HuGE Systematic Review and Meta-Analysis

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Abstract

Background

Studies investigating the associations between tumor necrosis factor-alpha (TNFA) polymorphisms and hepatocellular carcinoma (HCC) risk report conflicting results. We conducted a meta-analysis to assess the association between TNFA gene TNFA-308(G/A), TNFA-238(G/A), TNFA-863(C/A), TNFA-857(C/T), TNFA-1031 (T/C) polymorphisms and HCC susceptibility.

Methods

Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for TNFA polymorphisms and HCC were calculated in a fixed-effects model (the Mantel–Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.

Results

This meta-analysis included 17 case–control studies, which included 2,357 HCC cases and 3,161 controls. Overall, the variant genotypes AA/AG of -308G/A were associated with a significantly increased HCC risk, when compared with GG genotype (AA vs. GG, OR = 1.97, 95%CI = 1.01–3.83; AG vs. GG, OR = 1.88, 95%CI = 1.23–2.88; AA/AG vs. GG, OR = 1.80, 95%CI = 1.19–2.72). When stratifying for ethnicity, significantly elevated HCC risk was found among Asians. Moreover, similar results were observed between TNFA-238G/A, TNFA-863C/A polymorphisms and HCC risk among Asians (for -238G/A, AG vs. GG OR = 1.63, 95%CI = 1.17–2.26, AA/AG vs. GG OR = 1.61, 95%CI = 1.16–2.24; for -863 C/A, AC vs. CC OR = 1.72, 95%CI = 1.03–2.88, AA/AC vs. CC OR = 1.71, 95%CI = 1.02–2.86), while no associations were observed between TNFA-857C/T, TNFA-1031T/C polymorphisms and HCC susceptibility.

Conclusions

This meta-analysis shows that TNFA-308G/A, TNFA-238G/A and TNFA-863C/A polymorphisms may be associated with HCC among Asians. TNFA-857C/T and TNFA-1031T/C polymorphisms were not detected to be related to the risk for HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

OR:

Odds ratio

CI:

Confidence interval

TNFA:

Tumor necrosis factor-alpha

SNPs:

Single nucleotide polymorphisms

HWE:

Hardy–Weinberg equilibrium

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 30901720).We would like to thank the anonymous reviewer and the editor for their constructive comments on revising this manuscript.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Liver and Vascular Surgery, West China Hospital, Sichuan University, 37 Guo Xue Road, 610041, Chengdu, Sichuan Province, China

    Yonggang Wei, Fei Liu, Bo Li, Xi Chen, Yu Ma, Lvnan Yan, Tianfu Wen, Mingqing Xu, Wentao Wang & Jiayin Yang

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  1. Yonggang Wei
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  2. Fei Liu
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  3. Bo Li
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  4. Xi Chen
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  7. Tianfu Wen
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  10. Jiayin Yang
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Corresponding author

Correspondence to Bo Li.

Additional information

Wei Yonggang and Liu Fei contributed equally to this study.

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Wei, Y., Liu, F., Li, B. et al. Polymorphisms of Tumor Necrosis Factor-Alpha and Hepatocellular Carcinoma Risk: A HuGE Systematic Review and Meta-Analysis. Dig Dis Sci 56, 2227–2236 (2011). https://doi.org/10.1007/s10620-011-1617-y

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