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亚洲人群中TP53的mRNA表达及TP53密码子72 Arg/Pro基因多态性与结直肠癌风险的关联:一项生物信息学分析和荟萃分析

Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

作者信息

Dong Zhiyong, Zheng Longzhi, Liu Weimin, Wang Cunchuan

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Department of Surgery, The Affiliated Hospital of Putian University, Putian, China.

出版信息

Cancer Manag Res. 2018 May 25;10:1341-1349. doi: 10.2147/CMAR.S164892. eCollection 2018.

Abstract

BACKGROUND

The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations.

METHODS

The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI.

RESULTS

We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, =0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, =0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, =0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, =0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, <0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, =0.009).

CONCLUSION

TP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

摘要

背景

在亚洲人群中,TP53基因第72位密码子Pro/Arg基因多态性与结直肠癌风险之间的关系仍存在争议,因此进行了这项生物信息学分析和荟萃分析以评估两者之间的关联。

方法

从PubMed中检索关联研究,并纳入符合条件的报告。使用RevMan 5.3.1软件、Oncolnc、cBioPortal和Oncomine在线工具进行统计分析。荟萃分析采用随机/固定效应模型。数据以风险比或均值差及相应的95%置信区间报告。

结果

基于癌症基因组图谱数据库,我们证实TP53与结直肠癌相关,TP53的改变频率为53%的突变和7%的深度缺失,且TP53 mRNA表达在不同类型的结直肠癌中有所不同。然后,纳入了18项研究,这些研究探讨了TP53基因第72位密码子多态性与亚洲人群结直肠癌风险的关联。荟萃分析表明,TP53的Pro等位基因和Pro/Pro基因型与亚洲人群的结直肠癌风险相关,但Arg/Arg基因型不相关(Pro等位基因:比值比[OR]=1.20,95%置信区间:1.06至1.35,P=0.003;Pro/Pro基因型:OR=1.39,95%置信区间:1.15至1.69,P=0.0007;Arg/Arg基因型:OR=0.86,95%置信区间:0.74至1.00,P=0.05)。有趣的是,在基于人群研究的对照的荟萃分析中,我们发现TP53基因第72位密码子Pro/Arg基因多态性与结直肠癌风险相关(Pro等位基因:OR=1.33,95%置信区间:1.15至1.55,P=0.0002;Pro/Pro基因型:OR=1.61,95%置信区间:1.28至2.02,P<0.0001;Arg/Arg基因型:OR=0.77,95%置信区间:0.63至0.93,P=0.009)。

结论

TP53与结直肠癌相关,但mRNA表达的不同水平与结肠癌和直肠癌的生存率无关。TP53的Pro等位基因和Pro/Pro基因型与亚洲人群的结直肠癌风险相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac4e/5973318/e687f7556f2f/cmar-10-1341Fig1.jpg

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