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TNFalpha-308 G/A 多态性与乳腺癌风险相关:一项包含 10184 例病例和 12911 例对照的荟萃分析。

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

机构信息

State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.

出版信息

Breast Cancer Res Treat. 2010 Jul;122(1):267-71. doi: 10.1007/s10549-009-0698-1. Epub 2009 Dec 25.

Abstract

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.

摘要

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。

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