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

Abstract

Tumor necrosis factor a (TNFa) is a pleiotropic cytokine which can regulate a wide variety of cellular responses. Low concentrations of TNFa seem to increase tumor growth and progression. The -308 G/A polymorphism in TNFa 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 TNFa -308 G/A polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the TNFa -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 TNFa -308 G allele is a risk factor for developing breast cancer, especially for Caucasians.

Association between the TNF-α-238G>A and TGF-β1 L10P Polymorphisms and Breast Cancer Risk: A Meta-Analysis

“…Only published studies with available full text articles were included. When overlapping data of the same patient population were included in more than 1 publication, only the literature providing the full text was used in the analysis [2].…”

“…So far, the polymorphism TNF-a-238G>A, rs361525 has not been investigated and its relationship with cancer risk has not been understood compared to another important polymorphism, TNF-a-308G/A. In a recent study by Fang et al [2], the association between TNF-a-308G/A and breast tumor risk was confirmed through a meta-analysis. However, the accumu- Guo/Meng/Pei/Zhu tween TNF-a-238G>A and breast cancer risk in Asian women are warranted.…”

Association of the tumor necrosis factor-alpha -308G>A polymorphism with breast cancer in Mexican women

“…Furthermore, TNF-α induces the expression of adhesion molecules, facilitating the invasion of metastatic tumor cells (Champ et al, 2012). Multiple studies have found a significant association between this cytokine and increased risk for BC (Fang et al, 2010;Shen et al, 2011), and an increase in the severity of the disease (Azmy et al, 2004).…”

“…The TNF-α-308G>A polymorphism is located in the promoter region of the gene and involves the substitution of a guanine (G) by an adenine (A). This change effects gene expression, increasing production of TNF-α (Cereda et al, 2012) and has been extensively associated with complex diseases, including BC (Azmy et al, 2004;Fang et al, 2010;Shen et al, 2011).…”

The Lymphotoxin-α 252 A>G Polymorphism and Breast Cancer: A Meta-analysis

“…TNF-α and LTA polymorphisms were reported to be associated with cancers (Pooja et al, 2010), which had draw many researchers' attentions to in the breast cancer study. Recently, TNF-α polymorphisms were not found to be associated with the risk of BC in two meta-analysis studies (Fang et al, 2010). However, the results were inconsistent and ambiguous for LTA-252 A>G polymorphism studies (the most investigated site) (Park et al, 2002;KamaliSarvestani et al, 2005;Lee et al, 2005;Gaudet et al, 2007;Kohaar et al, 2009;Pooja et al, 2010;Karakus et al, 2011).…”