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

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Tumor Biology

Abstract

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.

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Correspondence to Hui Kang.

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Jin, G., Zhao, Y., Sun, S. et al. Association between the tumor necrosis factor alpha gene −308G> A polymorphism and the risk of breast cancer: a meta-analysis. Tumor Biol. 35, 12091–12098 (2014). https://doi.org/10.1007/s13277-014-2510-z

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  • DOI: https://doi.org/10.1007/s13277-014-2510-z

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