Polymorphisms of Tumor Necrosis Factor-Alpha and Hepatocellular Carcinoma Risk: A HuGE Systematic Review and Meta-Analysis
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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.
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.
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.
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.
KeywordsHepatocellular carcinoma TNFA Gene polymorphism Meta-analysis
Hepatitis B virus
Hepatitis C virus
Tumor necrosis factor-alpha
Single nucleotide polymorphisms
- 25.Yang Y, Luo C, Feng R, Bi S. The TNF-α, IL-1B and IL-10 polymorphisms and risk for hepatocellular carcinoma: A meta-analysis. J Cancer Res Clin Oncol. 2010; doi:10.1007/s00432-010-0959-8.
- 28.Petitti DB. Meta-analysis, decision analysis, and cost-effectiveness analysis: Methods for quantitative synthesis in medicine. 2nd ed. New York, NY: Oxford University Press; 2000.Google Scholar
- 34.Song SF, Gao YH, Gao YH, Chen SD, Chen SD. Interaction of TNF-α-308 and environmental risk factors in primary liver cancer. J Guangdong Pharm College. 2009;25:196–201. [Article in Chinese].Google Scholar
- 35.Huang HL, Huang HL, Xie JS, Xie JS, Huang ZS, Zhao QZ. The relationship of polymorphism of tumor necrosis factor-α gene promoter -238G/A with primary hepatic carcinoma in patients. Prog Anat Sci. 2007;13:11–13. [Article in Chinese].Google Scholar
- 36.Qiu B. Association study of gene polymorphisms and expression of TNF-α, TAP with hepatocellular carcinoma. Available at: http://dlib3.edu.cnki.net/kns50/detail.aspx?QueryID=17&CurRec=1. 2010 June 1 [Article in Chinese].
- 40.Jeng JE, Tsai HR, Chuang LY, et al. Independent and additive interactive effects among tumor necrosis factor-alpha polymorphisms, substance use habits, and chronic hepatitis B and hepatitis C virus infection on risk for hepatocellular carcinoma. Medicine (Baltimore). 2009;88:349–357.CrossRefGoogle Scholar