Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis.
Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis.
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GSTM1 和 GSTT1 的无效基因型会增加宫颈肿瘤的风险：基于证据的荟萃分析
DOI：
10.1371/journal.pone.0020157
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Gao LB;Pan XM;Li LJ;Liang WB;Bai P;Rao L;Su XW;Wang T;Zhou B;Wei YG;Zhang L
背景与目的谷胱甘肽S-转移酶（Glucosyls-transferases，GSTs）是一种多功能酶，在氧化应激的内源性产物和外源性致癌物的解毒过程中发挥重要作用。方法检索PubMed、EMBASE、ISI Web of Science和CBM数据库，共纳入25篇文献，其中23篇评价GSTM 1，19篇评价GSTT 1。粗比值比和相应的95%置信区间用于评估GSTM 1和GSTT 1多态性与宫颈肿瘤风险之间的关联。根据病理史、种族、基因分型DNA来源、质量评分和匹配变量进行亚组分析。结果GSTM 1和GSTT 1多态性的缺失基因型与宫颈癌发病风险显著增加相关（GSTM 1：OR = 1.40; 95%CI，1.19-1.65; GSTT 1：OR = 1.30; 95%CI，1.05-1.62）。 亚组分析表明，GSTM 1的无效基因型增加亚洲人宫颈肿瘤的风险，从白色血细胞和组织样本中分离DNA的研究，高质量和低质量的研究，以及匹配的研究。在GSTM 1-GSTT 1交互作用分析中，具有双重无效基因型的个体与宫颈肿瘤的风险显著增加相关（OR = 1.72，95%CI，1.18-2.51）。 结论GSTM 1和GSTT 1基因多态性，尤其是GSTM 1-GSTT 1基因多态性在宫颈癌的发生发展中可能起重要作用。由于研究间存在明显的异质性，数据未经调整，且本荟萃分析的样本量相对较小，因此应采用保守的方式来解释这些结果。设计良好的大样本研究对证实这些结果具有重要价值。
Background and Objectives Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens. Methods In this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable. Results The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19–1.65; for GSTT1: OR = 1.30; 95%CI, 1.05–1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18–2.51). Conclusion These findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.