谷胱甘肽 S-转移酶 Pi 1（GSTP1）基因 313 A/G（rs1695）多态性与膀胱癌风险相关：基于 34 项病例对照研究的系统评价和荟萃分析证据。

Glutathione S-Transferase Pi 1 (GSTP1) Gene 313 A/G (rs1695) polymorphism is associated with the risk of urinary bladder cancer: Evidence from a systematic review and meta-analysis based on 34 case-control studies.

机构信息

Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, China.

Department of Central Laboratory & Institute of Clinical Molecular Biology and Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China.

出版信息

Gene. 2019 Nov 30;719:144077. doi: 10.1016/j.gene.2019.144077. Epub 2019 Aug 24.

DOI:10.1016/j.gene.2019.144077

PMID:31454540

Abstract

BACKGROUND

Glutathione S-transferases (GSTs) contain a series of critical enzymes regulating proliferation or apoptosis in the tumor microenvironment. Data from publications about the correlation between Glutathione S-transferase Pi 1 (GSTP1) gene 313 A/G (rs1695) polymorphism and bladder caner (BCa) remained controversial. To explore the exact correlation between this polymorphism and the development of BCa, we carried out this study.

MATERIALS AND METHODS

All relevant publications from Pubmed, Web of Science, Cochrane Library, PMC, Embase and Wanfang databases (from building to March 30th, 2019) were retrieved. This meta-analysis was carried out by utilizing STATA software.

RESULTS

34 case-control studies with 15,704 participants recruiting 7236 BCa patients and 8468 healthy controls were ultimately analyzed in our study. The pooling results indicated that GSTP1 gene 313 A/G (rs1695) polymorphism was obviously related to BCa (GG vs AA: OR = 1.33, 95%CI = 1.04-1.69). Similar results were found in the association between this polymorphism and transitional cell carcinoma (TCC) risk (GG vs AA: OR = 1.95, 95%CI = 1.18-3.23). Furthermore, we revealed an increased association between the GG genotype and BCa in Asians (GG vs AA: OR = 2.04, 95%CI = 1.09-3.79), while no correlation was revealed in Caucasians. As to different tumor grades or stages, this polymorphism was considered to elevate low grade BCa development and null results were uncovered with high grade BCa.

CONCLUSION

This study indicated that GSTP1 gene 313 A/G (rs1695) polymorphism increased the susceptibility to BCa, particularly to TCC. In addition, this study found that this polymorphism was obviously related to elevated BCa risk in Asian population and also increased low grade BCa risk. Results based on the five genetic models indicated that GSTP1 G-allele might be the susceptibility gene and GG genotype might be the susceptibility genotype.

摘要

背景

谷胱甘肽 S-转移酶（GSTs）包含一系列调节肿瘤微环境中增殖或凋亡的关键酶。关于谷胱甘肽 S-转移酶 Pi 1（GSTP1）基因 313 A/G（rs1695）多态性与膀胱癌（BCa）之间相关性的文献数据仍然存在争议。为了探讨这种多态性与 BCa 发展的确切相关性，我们进行了这项研究。

材料和方法

从 Pubmed、Web of Science、Cochrane Library、PMC、Embase 和万方数据库（从建立到 2019 年 3 月 30 日）中检索到所有相关出版物。本荟萃分析使用 STATA 软件进行。

结果

共纳入了 34 项病例对照研究，共纳入了 15704 名参与者，其中包括 7236 名 BCa 患者和 8468 名健康对照者。汇总结果表明，GSTP1 基因 313 A/G（rs1695）多态性与 BCa 明显相关（GG 与 AA：OR=1.33，95%CI=1.04-1.69）。在这种多态性与移行细胞癌（TCC）风险的相关性中也发现了类似的结果（GG 与 AA：OR=1.95，95%CI=1.18-3.23）。此外，我们还发现 GG 基因型与亚洲人群 BCa 的相关性增加（GG 与 AA：OR=2.04，95%CI=1.09-3.79），而在高加索人群中则没有相关性。至于不同的肿瘤分级或分期，这种多态性被认为会增加低级别 BCa 的发展，而高级别 BCa 则未发现有相关性。

结论

本研究表明，GSTP1 基因 313 A/G（rs1695）多态性增加了 BCa 的易感性，特别是对 TCC。此外，本研究发现，这种多态性与亚洲人群中 BCa 风险的增加明显相关，也增加了低级别 BCa 的风险。基于五种遗传模型的结果表明，GSTP1 G 等位基因可能是易感基因，GG 基因型可能是易感基因型。