Null Genotypes of GSTM1 and GSTT1 Contribute to Risk of Cervical Neoplasia: An Evidence-Based Meta-Analysis

Background and ObjectivesGlutathione 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. MethodsIn 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. ResultsThe 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). ConclusionThese 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.背景与研究目的：谷胱甘肽S-转移酶（Glutathione S-transferases, GSTs）是一类多功能酶，在氧化应激内源性产物与外源性致癌物的解毒过程中发挥关键作用。研究方法：本荟萃分析（meta-analysis）通过检索PubMed、EMBASE、ISI Web of Science以及中国生物医学文献数据库（CBM），共筛选纳入25项相关研究，其中23项评估了GSTM1基因多态性，19项评估了GSTT1基因多态性。本研究采用粗比值比（crude odds ratios）及其对应的95%置信区间（confidence intervals, CI），分析GSTM1与GSTT1基因多态性与宫颈肿瘤（cervical neoplasia）发生风险的关联。此外，本研究依据病理病史、种族、DNA基因分型的样本来源、研究质量评分以及匹配变量开展亚组分析。研究结果：GSTM1与GSTT1基因的空白基因型可显著升高宫颈肿瘤的发生风险：其中GSTM1空白基因型的比值比OR=1.40，95%CI为1.19~1.65；GSTT1空白基因型的OR=1.30，95%CI为1.05~1.62。亚组分析显示，在亚洲人群、以白细胞及组织样本提取DNA的研究、高质量与低质量研究以及匹配设计研究中，GSTM1空白基因型均可显著升高宫颈肿瘤发生风险。在GSTM1与GSTT1的交互作用分析中，同时携带两种基因空白基因型的个体，其宫颈肿瘤发生风险显著升高（OR=1.72；95%CI：1.18~2.51）。研究结论：本研究结果表明，GSTM1与GSTT1基因多态性，尤其是二者的交互作用，可能在宫颈肿瘤的发生发展中发挥关键作用。鉴于本荟萃分析纳入研究间存在显著异质性、未进行校正分析且样本量相对较小，因此对本研究结果的解读应持保守态度。未来需开展设计严谨、样本量更大的研究以验证本研究结论。