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CYP3A4和CYP3A5基因多态性与癌症风险之间的关联:一项荟萃分析和荟萃回归分析

Association between the CYP3A4 and CYP3A5 polymorphisms and cancer risk: a meta-analysis and meta-regression.

作者信息

He Xiao-Feng, Liu Zhi-Zhong, Xie Jian-Jun, Wang Wei, Du Ya-Ping, Chen Yu, Wei Wu

机构信息

Department of Research, Peace Hospital of Changzhi Medical College, Changzhi, 046000, People's Republic of China.

出版信息

Tumour Biol. 2014 Oct;35(10):9859-77. doi: 10.1007/s13277-014-2241-1. Epub 2014 Jul 4.

DOI:10.1007/s13277-014-2241-1
PMID:24989928
Abstract

Previously published data on the association between CYP3A4 A392G and CYP3A5 Met235Thr polymorphisms and the risk of cancer remained controversial. Thus, we performed a meta-analysis to investigate the association between cancer susceptibility and CYP3A4 A392G (18,629 cases and 22,323 controls from 49 studies) and CYP3A5 Met235Thr polymorphisms (14,334 cases and 18,183 from 39 studies) in different inheritance models. We used odds ratios with 95 % confidence intervals to assess the strength of the association. Overall, significant association was found between CYP3A4 A392G polymorphism and cancer susceptibility (dominant model, odds ratio (OR) = 1.19; 95 % confidence interval (CI) = 1.03-1.38). In the further stratified and sensitivity analyses, significant increased prostate cancer risk was found among Caucasians (dominant model, OR = 1.88; 95 % CI = 1.20-2.95; recessive model, OR = 2.10; 95 % CI = 1.23-3.60; additive model, OR = 1.80, 95 % CI = 1.24-2.63; homozygous model, OR = 2.34, 95 % CI = 1.36-4.03; heterozygote model, OR = 1.79, 95 % CI = 1.11-2.89) for CYP3A4 A392G. For CYP3A5 Met235Thr polymorphism, no significant association was found among overall analysis and any subgroup analysis. In summary, this meta-analysis suggests that CYP3A4 A392G polymorphism is associated with increased prostate cancer risk among Caucasians and CYP3A5 Met235Thr polymorphism is not associated with the risk of cancer.

摘要

先前发表的关于细胞色素P450 3A4(CYP3A4)A392G和细胞色素P450 3A5(CYP3A5)Met235Thr基因多态性与癌症风险之间关联的数据仍存在争议。因此,我们进行了一项荟萃分析,以研究癌症易感性与CYP3A4 A392G(来自49项研究的18629例病例和22323例对照)以及CYP3A5 Met235Thr基因多态性(来自39项研究的14334例病例和18183例对照)在不同遗传模型中的关联。我们使用比值比及其95%置信区间来评估关联强度。总体而言,发现CYP3A4 A392G基因多态性与癌症易感性之间存在显著关联(显性模型,比值比(OR)=1.19;95%置信区间(CI)=1.03 - 1.38)。在进一步的分层分析和敏感性分析中,发现CYP3A4 A392G基因多态性在高加索人群中显著增加前列腺癌风险(显性模型,OR = 1.88;95% CI = 1.20 - 2.95;隐性模型,OR = 2.10;95% CI = 1.23 - 3.60;加性模型,OR = 1.80,95% CI = 1.24 - 2.63;纯合子模型,OR = 2.34,95% CI = 1.36 - 4.03;杂合子模型,OR = 1.79,95% CI = 1.11 - 2.89)。对于CYP3A5 Met235Thr基因多态性,在总体分析和任何亚组分析中均未发现显著关联。总之,这项荟萃分析表明,CYP3A4 A392G基因多态性与高加索人群中前列腺癌风险增加相关,而CYP3A5 Met235Thr基因多态性与癌症风险无关。

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