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CCND1基因c.870G>A多态性与乳腺癌风险的关联:一项病例对照研究及荟萃分析

Association of CCND1 Gene c.870G>A Polymorphism with Breast Cancer Risk: A Case-ControlStudy and a Meta-Analysis.

作者信息

Soleimani Zahra, Kheirkhah Davood, Sharif Mohammad Reza, Sharif Alireza, Karimian Mohammad, Aftabi Younes

机构信息

Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran.

Trauma Research Center, Kashan University of Medical Sciences, Kashan, Iran.

出版信息

Pathol Oncol Res. 2017 Jul;23(3):621-631. doi: 10.1007/s12253-016-0165-3. Epub 2016 Dec 21.

Abstract

Cyclin D1 (CCND1) plays an essential role in regulating the progress of the cell cycle from G1 to S phase. There is a common c.870G>A polymorphism in the CCND1 gene. The aim of this study was to investigate the association of CCND1 gene c.870G>A polymorphism with breast cancer risk in a case-control study, which followed by a meta-analysis and an in silico analysis. Three hundred and thirty-five subjects composed of 174 women with breast cancer and 161 healthy controls were included in the case-control study. CCND1 gene c.870G>A genotyping was performed by PCR-RFLP. Meta-analysis was done for 14 studies composed of 7281 cases and 6820 controls. Some bioinformatics tools were applied to investigate the effects of c.870G>A on the mRNA splicing and structure. Our data obtained from case-control study revealed that GA genotype (OR: 1.89, 95%CI: 1.12-3.17, p = 0.017), AA genotype (OR: 1.95, 95%CI: 1.08-3.53, p = 0.027), and A allele (OR: 1.44, 95%CI: 1.06-1.95, p = 0.019) were significantly associated with breast cancer risk. The results of meta-analysis showed a significant association between CCND1 c.870G>A polymorphism and breast cancer risk, especially in Caucasian population. In silico analysis revealed that c.870G>A transition affect CCND1 mRNA splicing and secondary structure.

摘要

细胞周期蛋白D1(CCND1)在调控细胞周期从G1期进入S期的进程中起着至关重要的作用。CCND1基因存在一种常见的c.870G>A多态性。本研究的目的是在一项病例对照研究中调查CCND1基因c.870G>A多态性与乳腺癌风险的关联,随后进行荟萃分析和计算机模拟分析。病例对照研究纳入了335名受试者,其中包括174名乳腺癌女性患者和161名健康对照。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对CCND1基因c.870G>A进行基因分型。对由7281例病例和6820例对照组成的14项研究进行了荟萃分析。应用了一些生物信息学工具来研究c.870G>A对mRNA剪接和结构的影响。我们从病例对照研究中获得的数据显示,GA基因型(比值比:1.89, 95%置信区间:1.12 - 3.17, p = 0.017)、AA基因型(比值比:1.95, 95%置信区间:1.08 - 3.53, p = 0.027)和A等位基因(比值比:1.44, 95%置信区间:1.06 - 1.95, p = 0.019)与乳腺癌风险显著相关。荟萃分析结果显示CCND1 c.870G>A多态性与乳腺癌风险之间存在显著关联,尤其是在白种人群中。计算机模拟分析表明c.870G>A转换会影响CCND1 mRNA的剪接和二级结构。

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