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

Abstract

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.

Meta-Analysis Shows Strong Positive Association of the TNF-α Gene with Tumor Stage in Bladder Cancer

“…Although genotype changes at position –308 of the TNF- α promoter are frequently observed in several cancers [18,19,20], in the subgroup analysis according to the source of controls and ethnicity, no significantly statistical evidence was found for healthy and benign control among Asian and Caucasian subjects in various statistical models for the association between –308 G/A polymorphism and bladder cancer risk. The results of this meta-analysis were consistent with the meta-analysis results of some types of cancer [21], but inconsistent with other meta-analyses [22]. It is conceivable that different types of cancer have different etiopathogeneses.…”

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

“…In our population, the frequency of this polymorphism was 14% in BC patients and 1% in controls and was identified as a risk factor. Other studies have observed the association between the -308G>A polymorphism and BC (Li et al, 2008;Pooja et al, 2011;Shen et al, 2011).…”

“…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).…”

Association between TNF-α-308G>A and -238G>A gene polymorphisms and TNF-α serum levels in Mexican colorectal cancer patients

“…The rs361525 minor allele is only present in the heterozygous genotype, and has previously been reported to be present at a frequency of 0.1-0.2%, based on different population data (Mohamed et al, 2010;Vázquez-Huerta et al, 2014). Although these polymorphisms have been connected to various diseases, including CRC (Fan et al, 2011;Shen et al, 2011;Cereda et al, 2012;Chu et al, 2012;Gómez Flores-Ramos et al, 2013;Stanilov et al, 2014;Vázquez-Huerta et al, 2014), study results have been inconsistent. The aim of this investigation was to measure TNF-α concentration in the plasma of Mexican CRC patients and determine its relationship with the -308G>A and -238G>A polymorphisms and haplotypes of the TNF-α gene.…”