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NFKB1基因-94位点插入/缺失ATTG启动子多态性与癌症风险的遗传关联:42项病例对照研究的荟萃分析

Genetic association between NFKB1 -94 ins/del ATTG Promoter Polymorphism and cancer risk: a meta-analysis of 42 case-control studies.

作者信息

Wang Duan, Xie Tianhang, Xu Jin, Wang Haoyang, Zeng Weinan, Rao Shuquan, Zhou Kai, Pei Fuxing, Zhou Zongke

机构信息

West China Hospital/West China School of Medicine, Sichuan University, Chengdu, 610041, China.

Tianjin Hospital, Tianjin, 300211, China.

出版信息

Sci Rep. 2016 Jul 22;6:30220. doi: 10.1038/srep30220.

Abstract

Accumulating evidences have indicated that the functional -94 ins/del ATTG polymorphism in the promoter region of human nuclear factor-kappa B1 (NFKB1) gene may be associated with cancer risk. However, some studies yielded conflicting results. To clarify precise association, we performed a comprehensive meta-analysis of 42 case-control studies involving 43,000 subjects (18,222 cases and 24,778 controls). The overall results suggested that the -94 ins/del ATTG polymorphism had a decreased risk for cancer, reaching significant levels in five genetic models (dominant model: OR = 0.86, 95% CI = 0.79-0.95, P = 0.002; recessive model: OR = 0.84, 95% CI = 0.74-0.94, P = 0.003; homozygous model: OR = 0.77, 95% CI = 0.66-0.90, P = 0.001; heterozygous model: OR = 0.90, 95% CI = 0.83-0.98, P = 0.011; allelic model: OR = 0.89, 95% CI = 0.83-0.96, P = 0.002). Furthermore, the -94 ins/del ATTG polymorphism could confer a decreased or increased risk for cancer development among Asians and Caucasians, respectively. Additionally, the stratification analysis revealed a significant association between the variant and decreased risk of oral, ovarian, and nasopharyngeal cancer in Asians. After we adjusted p values using the Benjamini-Hochberg false discovery rate method to account for multiple comparisons, these associations remained.

摘要

越来越多的证据表明,人类核因子-κB1(NFKB1)基因启动子区域功能性的-94 ins/del ATTG多态性可能与癌症风险相关。然而,一些研究得出了相互矛盾的结果。为了阐明确切的关联,我们对42项病例对照研究进行了全面的荟萃分析,涉及43000名受试者(18222例病例和24778例对照)。总体结果表明,-94 ins/del ATTG多态性降低了患癌风险,在五种遗传模型中达到显著水平(显性模型:OR = 0.86,95% CI = 0.79 - 0.95,P = 0.002;隐性模型:OR = 0.84,95% CI = 0.74 - 0.94,P = 0.003;纯合子模型:OR = 0.77,95% CI = 0.66 - 0.90,P = 0.001;杂合子模型:OR = 0.90,95% CI = 0.83 - 0.98,P = 0.011;等位基因模型:OR = 0.89,95% CI = 0.83 - 0.96,P = 0.002)。此外,-94 ins/del ATTG多态性分别可能使亚洲人和高加索人患癌风险降低或增加。此外,分层分析显示该变体与亚洲人口腔癌、卵巢癌和鼻咽癌风险降低之间存在显著关联。在我们使用Benjamini-Hochberg错误发现率方法调整P值以考虑多重比较后,这些关联仍然存在。

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