Tumor Biol. DOI 10.1007/s13277-014-2510-z
RESEARCH ARTICLE
Association between the tumor necrosis factor alpha gene −308G> A polymorphism and the risk of breast cancer: a meta-analysis Guojiang Jin & Yan Zhao & Shuang Sun & Hui Kang
Received: 27 May 2014 / Accepted: 14 August 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
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, Pheterogeneity A polymorphism and susceptibility to breast cancer in diverse populations [7–24]. However, the results of these studies are inconsistent and remain controversial. Therefore, in the present study, we performed a meta-analysis of all currently available publications considering the susceptibility of the TNF-α −308G> A polymorphism to breast cancer to provide a better understanding of the molecular mechanisms underlying breast carcinogenesis.
Materials and methods Identification of eligible studies We carried out a literature search of the PubMed, Embase, and Web of Science databases to identify individual studies conducted on the association between the TNF-α −308G> A polymorphism and breast cancer risk up to April 4, 2014. We used the following keywords and subject terms: “genetic polymorphism” or “polymorphism” or “SNP” or “gene mutation” or “genetic variants” and “breast neoplasms” or “breast cancer” or “breast tumor” or “breast carcinoma” and “tumor necrosis factor” or “TNF” or “−308G> A” or “TNF-α” or “rs1800629.” References of all primary studies and review articles were reviewed to obtain additional references. When multiple publications reported on the same or overlapping data, the largest or most complete study was chosen.
not reach a consensus, another investigator adjudicated over the disagreements. Statistical methods The strength of the association between the TNF-α −308G> A polymorphism and breast cancer risk was measured by ORs with corresponding 95 % CIs and was examined under four genetic models: the allele model (A vs. G), homozygous model (AA vs. GG), recessive model (AA vs. GG + GA), and dominant model (AA + GA vs. GG). We tested whether genotype frequencies of controls were in HWE using the χ2 test. The χ2-based Q (Cochran’s Q test) and I2 statistic tests were used for between-study heterogeneity analysis. Heterogeneity between studies was considered to be significant when P A polymorphism with breast cancer risk [7–24]. The study search process is shown in Fig. 1. If an article contained two or more ethnic groups, it was separated into different studies. Therefore, 19 case– control studies with a total of 27,470 subjects (12,360 cases and 15,110 controls) were finally included in this metaanalysis. Of these, three were conducted in Asian populations, 16 were in Caucasians, and one study was conducted in an African population. Sixteen studies were populationbased and four were hospital-based. The distribution of genotypes in the controls of all studies was consistent with HWE, with the exception of two studies [11, 21]. A list of details abstracted from the studies included in the metaanalysis is provided in Table 1.
Tumor Biol. Fig. 1 Flow diagram of studies included and excluded in the present meta-analysis
Articles identified after a comprehensive search of the PubMed, Web of Science, and Embase (April 17, 2014) (n=126) Studies excluded after reading the titles and abstracts: 50-Irrelevant papers 29-Not associated with the TNF-α -308G>A polymorphism and breast cancer 16-Reviews, letters, meta-analysis 6-Animal studies Articles on the TNF-α -308G>A polymorphism and breast cancer (n=25)
Studies excluded after reading the full texts: 1-Duplicated Publication 3-Insufficient information 3-Case-only study
Eligible publications included into our study (n=18)
Meta-analysis results Table 2 shows the main findings of this meta-analysis in detail. Overall, no significant associations were observed between the TNF-α −308G> A polymorphism and breast cancer risk for all genetic models (allele model OR=1.06, 95 % CI 0.90–1.24, Pheterogeneity
RESEARCH ARTICLE
Association between the tumor necrosis factor alpha gene −308G> A polymorphism and the risk of breast cancer: a meta-analysis Guojiang Jin & Yan Zhao & Shuang Sun & Hui Kang
Received: 27 May 2014 / Accepted: 14 August 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
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, Pheterogeneity A polymorphism and susceptibility to breast cancer in diverse populations [7–24]. However, the results of these studies are inconsistent and remain controversial. Therefore, in the present study, we performed a meta-analysis of all currently available publications considering the susceptibility of the TNF-α −308G> A polymorphism to breast cancer to provide a better understanding of the molecular mechanisms underlying breast carcinogenesis.
Materials and methods Identification of eligible studies We carried out a literature search of the PubMed, Embase, and Web of Science databases to identify individual studies conducted on the association between the TNF-α −308G> A polymorphism and breast cancer risk up to April 4, 2014. We used the following keywords and subject terms: “genetic polymorphism” or “polymorphism” or “SNP” or “gene mutation” or “genetic variants” and “breast neoplasms” or “breast cancer” or “breast tumor” or “breast carcinoma” and “tumor necrosis factor” or “TNF” or “−308G> A” or “TNF-α” or “rs1800629.” References of all primary studies and review articles were reviewed to obtain additional references. When multiple publications reported on the same or overlapping data, the largest or most complete study was chosen.
not reach a consensus, another investigator adjudicated over the disagreements. Statistical methods The strength of the association between the TNF-α −308G> A polymorphism and breast cancer risk was measured by ORs with corresponding 95 % CIs and was examined under four genetic models: the allele model (A vs. G), homozygous model (AA vs. GG), recessive model (AA vs. GG + GA), and dominant model (AA + GA vs. GG). We tested whether genotype frequencies of controls were in HWE using the χ2 test. The χ2-based Q (Cochran’s Q test) and I2 statistic tests were used for between-study heterogeneity analysis. Heterogeneity between studies was considered to be significant when P A polymorphism with breast cancer risk [7–24]. The study search process is shown in Fig. 1. If an article contained two or more ethnic groups, it was separated into different studies. Therefore, 19 case– control studies with a total of 27,470 subjects (12,360 cases and 15,110 controls) were finally included in this metaanalysis. Of these, three were conducted in Asian populations, 16 were in Caucasians, and one study was conducted in an African population. Sixteen studies were populationbased and four were hospital-based. The distribution of genotypes in the controls of all studies was consistent with HWE, with the exception of two studies [11, 21]. A list of details abstracted from the studies included in the metaanalysis is provided in Table 1.
Tumor Biol. Fig. 1 Flow diagram of studies included and excluded in the present meta-analysis
Articles identified after a comprehensive search of the PubMed, Web of Science, and Embase (April 17, 2014) (n=126) Studies excluded after reading the titles and abstracts: 50-Irrelevant papers 29-Not associated with the TNF-α -308G>A polymorphism and breast cancer 16-Reviews, letters, meta-analysis 6-Animal studies Articles on the TNF-α -308G>A polymorphism and breast cancer (n=25)
Studies excluded after reading the full texts: 1-Duplicated Publication 3-Insufficient information 3-Case-only study
Eligible publications included into our study (n=18)
Meta-analysis results Table 2 shows the main findings of this meta-analysis in detail. Overall, no significant associations were observed between the TNF-α −308G> A polymorphism and breast cancer risk for all genetic models (allele model OR=1.06, 95 % CI 0.90–1.24, Pheterogeneity
