Tumor Biology

, Volume 35, Issue 12, pp 12091–12098 | Cite as

Association between the tumor necrosis factor alpha gene −308G> A polymorphism and the risk of breast cancer: a meta-analysis

  • Guojiang Jin
  • Yan Zhao
  • Shuang Sun
  • Hui Kang
Research Article


The multifunctional cytokine tumor necrosis factor alpha (TNF-α) plays an important role in cell proliferation, differentiation, apoptosis, lipid metabolism, and endothelial function. To date, many studies have evaluated the association between the TNF-α −308G> A polymorphism and breast cancer risk; however, the results remain ambiguous and inconclusive. To derive a more precise estimation of the association and assess its strength, we carried out a meta-analysis of 20 published case–control studies with 12,360 cases and 15,110 controls using crude odd ratios (ORs) with 95 % confidence intervals (CIs). Overall, no significant associations were found for all genetic models (allele model OR = 1.06, 95 % CI 0.90–1.24, P heterogeneity < 0.001; homozygous model OR = 1.25, 95 % CI 0.85–1.82, P heterogeneity < 0.001; recessive model OR = 1.26, 95 % CI 0.88–1.82, P heterogeneity = 0.001; dominant model OR = 1.00, 95 % CI 0.85–1.18, P heterogeneity < 0.001). Moreover, no significant associations were observed when stratified by ethnicity, control source, genotyping method, or Hardy–Weinberg equilibrium status. However, in the menopausal status subgroup, significantly decreased breast cancer risks were found among postmenopausal women (allele model OR = 0.90, 95 % CI 0.83–0.98; dominant model OR = 0.89, 95 % CI 0.81–0.98), while the TNF-α −308 AA genotype was a breast cancer risk factor in premenopausal women (homozygous model OR = 4.38, 95 % CI 1.44–13.36; recessive model OR = 4.43, 95 % CI 1.47–13.42). This meta-analysis indicated that the TNF-α −308G> A polymorphism is not associated with breast cancer risk in the overall population but that the A allele may be a protective factor for breast cancer in postmenopausal women, and the AA genotype may be a breast cancer risk factor in premenopausal women.


Tumor necrosis factor alpha Breast cancer Polymorphism Meta-analysis 


Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Laboratory MedicineThe First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Liaoning Center for Disease Control and PreventionShenyangChina

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