TNFα-308 G/A polymorphism is associated with breast cancer risk: a meta-analysis involving 10,184 cases and 12,911 controls

Tumor necrosis factor alpha (TNF alpha) is a pleiotropic cytokine which can regulate a wide variety of cellular responses. Low concentrations of TNF alpha seem to increase tumor growth and progression. The -308 G/A polymorphism in TNF alpha has been implicated in breast cancer risk but the published data remain inconclusive. In order to derive a more precise estimation of the relationship, a meta-analysis was performed by searching PubMed, Web of Science, ScienceDirect, EBSCO, CNKI, and Chinese Biomedicine Database. 11 studies including 10,184 cases and 12,911 controls were collected for TNF alpha -308 G/A polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the TNF alpha -308 G/A polymorphism and breast cancer risk. The pooled ORs were performed for codominant model (GG versus AA; GA versus AA), dominant model (GG + GA versus AA), recessive model (GG versus GA + AA), and G allele versus A allele, respectively. Overall, significantly elevated breast cancer risk was found for recessive model (OR = 1.10, 95% CI = 1.04-1.17) and for G allele versus A allele (OR = 1.08, 95% CI = 1.02-1.14). In the subgroup analysis by ethnicity, significantly increased risks were also found among Caucasians for recessive model and for G allele versus A allele (for recessive model: OR = 1.10, 95% CI = 1.04-1.17; for G allele versus A allele: OR = 1.09, 95% CI = 1.03-1.14). However, no significant associations were found among Asians for all genetic models. In conclusion, this meta-analysis suggests that the TNF alpha -308 G allele is a risk factor for developing breast cancer, especially for Caucasians.