Tumor necrosis factor gene polymorphisms in breast cancer patients

Tumor necrosis factor-α (TNF-α) is an important pro-inflammatory cytokine in the development and progress in human cancer. TNF-α polymorphisms have been confirmed to influence the risk for several types of cancer, however, the associations between TNF-α polymorphisms and breast cancer (BC) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations regarding this point. Electronic searches of several databases were conducted for all online publications on the associations between TNF-α-238, -308, -857, -863, -1031, -1210 polymorphisms and BC through March 2011. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated to assess the strength of these associations in fixed- and random-effect models with Review manager 5.0. A total of 17 studies with 44,442 BC patients and 49,926 controls involved were identified. This meta-analysis showed no significant association between TNF-α-308 polymorphism and BC (AA + GA vs. GG: OR = 0.95, 95% CI = 0.82-1.09) in overall and (OR = 1.44, 95% CI = 0.61-3.40) Asian populations, however, a negative association was shown in Caucasian subgroup (OR = 0.91, 95% CI = 0.85-0.97). As regards the TNF-α-238 polymorphism, the OR values (95% CI) were 0.99 (0.94-1.05), 0.94 (0.78-1.14), and 1.00 (0.95-1.05) for the overall, Asian, and Caucasian studies, respectively. No significant associations were found for other polymorphisms. Furthermore, there was a coincidence in the sensitivity analysis of these associations. No publication bias was detected in this study. To sum up, no significant associations were found between the TNF-α-308, -238, -857, -863, -1031, -1210 polymorphisms and the risk for BC in overall populations, whereas a negative association was found between TNF-α-308 polymorphism and BC in Caucasian populations.

Section: Resultsmentioning

confidence: 99%

TNF-alpha polymorphisms and breast cancer

Feng

et al. 2011

“…Majority of the studies till date reported lack of association between TNF-a (-308 G[A) polymorphism and breast cancer [5,[19][20][21][26][27][28][29][30][31][32][33][34][35]. For example, a study on the TNFa (-308 G[A) polymorphism in a Korean population comprising 95 breast cancer cases and 190 controls, showed no association [19].…”

Section: Discussionmentioning

confidence: 97%

Role of ethnic variations in TNF-α and TNF-β polymorphisms and risk of breast cancer in India

Singh

Francis²,

Bid

et al. 2010

TNF-α and -β, the multi-functional pro-inflammatory cytokines, are known to play important roles in both tumor progression and destruction based on their concentrations. Growth factors and various stimuli such as cytokines regulate proliferation of the breast epithelial cells. Therefore, the polymorphisms in the genes encoding these signaling molecules could affect the risk of breast cancer. We have investigated selected genetic polymorphisms in TNF-α promoter (rs1800629, -308 G>A and rs361525, -238 G>A) and TNF-β intron 1 (rs909253, +252 A>G) in ethnically two different case-control groups from India. The study included 200 cases and 200 controls from an Indo-European (North Indian) group, and 265 cases and 237 controls from a Dravidian (South Indian) group. Genotyping of a total of 902 individuals was done by direct DNA sequencing. None of the polymorphisms showed significant association with breast cancer in the Indo-European group; however, all the three polymorphisms showed strong association with breast cancer in the Dravidian group. Further, sub-group analysis in the Indo-European group showed no significant difference between pre-menopausal cases and controls or between post-menopausal cases and controls at any of the loci analyzed. However, all the polymorphisms in the Dravidian group were significantly associated with pre-menopausal but not with post-menopausal breast cancer. In conclusion, TNF-α and -β polymorphisms are strongly associated with breast cancer in the Dravidian but not in the Indo-European group.

“…In total, 11 studies with 10,184 cases and 12,911 controls met the inclusion criteria and were used in the pooled analyses [11][12][13][14][15][16][17][18][19][20][21]. Table 1 lists the studies identified and their main characteristics.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Therefore, it is conceivable that the TNFa -308 G/A polymorphism may have relationship with the breast cancer risk. To date, a number of studies have investigated the role of TNFa -308 G/A polymorphism in breast cancer risk [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. However, the results of those studies remain inconclusive, potentially due to the possible small effect of the polymorphism on breast cancer risk or the relatively small sample size in each of published studies.…”

Section: Introductionmentioning

confidence: 99%

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

Fang

Yao

et al. 2009

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.