Ding Hao, Liu Wei, Yu Xinyuan, Wang Lei, Shao Lingmin, Yi Wei
Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P.R. China.
Int J Clin Exp Med. 2014 Nov 15;7(11):3904-14. eCollection 2014.
Previous studies have shown that the single nucleotide polymorphisms (SNPs) in Methylenetetrahydrofolate reductase (MTHFR) and Glutathione S-transferases (GSTs, including GSTM1, GSTT1) genes play an important role in determining the response of an individual to environmental pathogenesis and significantly relate to incidences of various human tumors, including brain tumors. However, these genes' polymorphisms on meningioma risk remains poorly understood. The relevant inferences from previous studies are hindered by their limited statistical power and conflicting results. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between these polymorphisms and human meningioma risk. A literature search for eligible studies published before January 1, 2014 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. Pooled odds ratios (OR) with their corresponding 95% confidence intervals (95% CI) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. Heterogeneity and publication bias were evaluated. All statistical analyses were conducted by using the software of STATA 12.0 (STATA Corporation, College Station, TX, USA). For MTHFR C677T (dbSNP: rs1801133) (C T) polymorphism, 9 individual case-control studies from six publications with 1,615 cases and 1,909 controls were obtained. For GSTM1 null polymorphism, there were 4 studies with 417 cases and 1,735 controls. For GSTT1 null polymorphism, there were 4 studies with 405 cases and 1,622 controls. The combined results for the MTHFR C677T show that carriers of the CT genotype may be associated with a higher meningioma risk (OR = 1.20, 95% CI 1.05-1.38, P = 0.009). Stratified analyses show that Caucasians have significantly higher risk if they carry the CT genotype of MTHFR (OR = 1.31, 95% CI 1.05-1.63, P = 0.02). Risk of Caucasians carrying TT + CT genotype is also significantly higher (OR = 1.27, 95% CI 1.02-1.58, P = 0.03). Risk of Caucasians carrying TT genotype is not significantly different compared to control population (OR = 0.96, 95% CI 0.69-1.34, P = 0.82). All of the enrolled studies about GSTM1/GSTT1 are on Caucasians. The pooled ORGSTM1 and ORGSTT1 were not significant in Caucasian population. These results indicate SNPs of MTHFR C677T are related to meningioma risk with ethnic differences. Caucasians carrying CT genotype of MTHFR C677T have significantly higher meningioma susceptibility. SNPs of GSTM1/GSTT1 are not related to meningioma risk.
以往研究表明,亚甲基四氢叶酸还原酶(MTHFR)和谷胱甘肽S-转移酶(GSTs,包括GSTM1、GSTT1)基因中的单核苷酸多态性(SNPs)在决定个体对环境致病因素的反应中起重要作用,且与包括脑肿瘤在内的各种人类肿瘤的发病率显著相关。然而,这些基因的多态性与脑膜瘤风险之间的关系仍知之甚少。以往研究的相关推论受到其有限的统计效力和相互矛盾结果的阻碍。本荟萃分析的目的是相对全面地阐述这些多态性与人类脑膜瘤风险之间的关联。我们在PubMed、Embase、Web of Science、Cochrane图书馆和中国知网数据库中检索了2014年1月1日前发表的符合条件的研究。根据异质性检验结果,采用固定效应模型或随机效应模型下的合并比值比(OR)及其相应的95%置信区间(95%CI)来评估关联强度。对异质性和发表偏倚进行了评估。所有统计分析均使用STATA 12.0软件(美国德克萨斯州大学站市STATA公司)进行。对于MTHFR C677T(dbSNP:rs1801133)(C→T)多态性,从六篇文献中获得了9项个体病例对照研究,共1615例病例和1909例对照。对于GSTM1无效多态性,有4项研究,共417例病例和1735例对照。对于GSTT1无效多态性,有4项研究,共405例病例和1622例对照。MTHFR C677T的合并结果显示,CT基因型携带者可能与较高的脑膜瘤风险相关(OR = 1.20,95%CI 1.05 - 1.38,P = 0.009)。分层分析显示,携带MTHFR的CT基因型的白种人风险显著更高(OR = 1.31,95%CI 1.05 - 1.63,P = 0.02)。携带TT + CT基因型的白种人风险也显著更高(OR = 1.27,95%CI 1.02 - 1.58,P = 0.03)。携带TT基因型的白种人与对照人群相比风险无显著差异(OR = 0.96,95%CI 0.69 - 1.34,P = 0.82)。所有纳入的关于GSTM1/GSTT1的研究均针对白种人。在白种人群中,合并的OR GSTM1和OR GSTT1均无显著性。这些结果表明,MTHFR C677T的SNPs与脑膜瘤风险相关,存在种族差异。携带MTHFR C677T的CT基因型的白种人脑膜瘤易感性显著更高。GSTM1/GSTT1的SNPs与脑膜瘤风险无关。