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

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.