Polymorphisms of tumor necrosis factor-alpha and breast cancer risk: a meta-analysis

We conducted a meta-analysis to assess the association between tumor necrosis factor-alpha (TNF-alpha) gene TNFA −308 (G>A), TNFA −238 (G>A), TNFA −857 (C>T), TNFA −863 (C>A), TNFA −1031 (T>C), TNFA −1210 (A>T) polymorphisms and breast cancer(BC) susceptibility. We also performed subgroup analyses based on ethnicity (Caucasian, Asian, and African). An extensive search was performed to identify all case–control studies investigating such association. Thirteen eligible studies, including 10,236 BC patients and 13,143 controls, were identified. No significant association was observed in all genotypes in worldwide populations, but stratification by ethnicity indicated that the TNFA −308 A allele was associated with a decreased risk of BC compared with the G allele in Caucasian individuals (OR = 0.927, 95%CI = 0.879–0.978). Similar results were obtained when the A/A +A/G genotype was compared with the G/G genotype. In addition, meta-analysis results indicated that the A/A genotype of TNFA −308 was a risk factor for BC in African (A/A vs. G/G OR = 4.085 95%CI = 1.460–11.425; A/A vs. G/A OR = 4.861 95%CI = 1.746–13.527; A/A vs. G/A + G/G OR = 4.246 95%CI = 1.551–11.625), but not in Caucasian or Asian individuals. In conclusion, the results of this meta-analysis indicate that the TNFA −308 A allele may be an important protective factor for BC in European individuals, but it is not likely to confer susceptibility to BC in worldwide populations. In addition, the AA genotype of TNFA −308 may be a risk factor for BC in African individuals. Besides, other polymorphisms were not associated with BC susceptibility.