State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
Breast Cancer Res Treat. 2010 Jul;122(1):267-71. doi: 10.1007/s10549-009-0698-1. Epub 2009 Dec 25.
Tumor necrosis factor alpha (TNFalpha) is a pleiotropic cytokine which can regulate a wide variety of cellular responses. Low concentrations of TNFalpha seem to increase tumor growth and progression. The -308 G/A polymorphism in TNFalpha 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 TNFalpha -308 G/A polymorphism. Crude ORs with 95% CIs were used to assess the strength of association between the TNFalpha -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 TNFalpha -308 G allele is a risk factor for developing breast cancer, especially for Caucasians.
肿瘤坏死因子-α(TNFalpha)是一种多效细胞因子,可以调节广泛的细胞反应。低浓度的 TNFalpha 似乎会增加肿瘤的生长和进展。TNFalpha 的-308 G/A 多态性与乳腺癌风险有关,但已发表的数据仍不确定。为了更准确地评估这种关系,我们通过搜索 PubMed、Web of Science、ScienceDirect、EBSCO、CNKI 和中国生物医学数据库进行了荟萃分析。共纳入了 11 项研究,包括 10184 例病例和 12911 例对照,用于 TNFalpha-308 G/A 多态性分析。使用粗 OR 值和 95%CI 来评估 TNFalpha-308 G/A 多态性与乳腺癌风险之间的关联强度。分别进行了共显性模型(GG 与 AA;GA 与 AA)、显性模型(GG+GA 与 AA)、隐性模型(GG 与 GA+AA)和 G 等位基因与 A 等位基因模型的汇总 OR 值分析。总体而言,隐性模型(OR=1.10,95%CI=1.04-1.17)和 G 等位基因与 A 等位基因(OR=1.08,95%CI=1.02-1.14)与乳腺癌风险显著相关。在按种族亚组分析中,也发现白种人中隐性模型和 G 等位基因与 A 等位基因与乳腺癌风险显著增加(隐性模型:OR=1.10,95%CI=1.04-1.17;G 等位基因与 A 等位基因:OR=1.09,95%CI=1.03-1.14)。然而,在亚洲人群中,所有遗传模型均未发现显著相关性。综上所述,这项荟萃分析表明,TNFalpha-308 G 等位基因是发生乳腺癌的一个危险因素,尤其是在白种人群中。