GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: A comprehensive meta-analysis
GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: A comprehensive meta-analysis
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DOI：
10.1016/j.ejca.2010.02.009
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发表时间：
2010-06-01
影响因子：
8.4
通讯作者：
Sergentanis, Theodoros N.
中科院分区：
文献类型：
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作者：
Economopoulos, Konstantinos P.;Sergentanis, Theodoros N.
谷胱甘肽S转移酶(GSTs)催化谷胱甘肽与具有亲电中心的亲脂化合物之间的反应，导致有毒化合物、外源化合物和氧化应激产物的中和。GST多态(GSTM1缺失/现型、GSTT1缺失/现型、GSTP1Ile105Val和GSTA1*A/*B)是否代表结直肠癌的危险因素存在争议。这项荟萃分析旨在研究上述基因多态与结直肠癌风险之间的关系。符合条件的GSTM1研究44项(11,998例结直肠癌患者，17552名对照)，GSTT1 34项研究(8596例，13,589名对照)，19项GSTP1研究(5421例，7671名对照)和4项GSTA1多态性研究(1648例，2039名对照)。合并优势比(OR)适当地从固定效应或随机效应模型中得出。对高加索人和中国人进行了单独的分析。在适当的情况下，对对照中的基因型频率偏离Hardy-Weinberg平衡进行了敏感性分析。高加索人群中GSTM1缺失等位基因携带者患结直肠癌的风险增加(合并OR=1.150，95%可信区间：1.060~1.248，随机效应)；在中国人群中未发现显著关联(合并OR=1.025，95%CI：0.903~1.163，固定效应)。同样，GSTT1零等位基因携带者在高加索人群中患结直肠癌的风险增加(合并OR=1.312，95%CI：1.119-1.538，随机效应)；在中国受试者中这种关联不显著(合并OR=1.068，95%CI：0.788-1.449，随机效应)。关于GSTP1，Ile105Val在两个种族中都没有显着性关联。GSTA1*A/*B基因多态性与结直肠癌风险无关。在高加索人群中，GSTM1和GSTT1缺失基因型增加了患结直肠癌的风险。(C)2010爱思唯尔有限公司。保留所有权利。
Glutathione S-transferases (GSTs) catalyse reactions between glutathione and lipophilic compounds with electrophilic centres, leading to neutralisation of toxic compounds, xenobiotics and products of oxidative stress. Controversy exists about whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, GSTP1 Ile105Val and GSTA1*A/*B) represent risk factors for colorectal cancer. This meta-analysis aims to examine the associations between the above-mentioned polymorphisms and colorectal cancer risk. Forty-four studies were eligible for GSTM1 (11,998 colorectal cancer cases, 17,552 controls), 34 studies for GSTT1 (8596 cases, 13,589 controls), 19 studies for GSTP1 (5421 cases, 7671 controls) and four studies for GSTA1 polymorphism (1648 cases, 2039 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Separate analyses were conducted on Caucasian and Chinese populations. Where appropriate, sensitivity analysis concerning the deviation of genotype frequencies in controls from the Hardy-Weinberg equilibrium was performed. GSTM1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR = 1.150, 95% confidence interval (CI): 1.060-1.248, random effects); no significant association was detected for Chinese subjects (pooled OR = 1.025, 95% CI: 0.903-1.163, fixed effects). Similarly, GSTT1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR = 1.312, 95% CI: 1.119-1.538, random effects); the association in Chinese subjects was not significant (pooled OR = 1.068, 95% CI: 0.788-1.449, random effects). Concerning GSTP1 Ile105Val no significant associations were demonstrated in either race. GSTA1*A/*B polymorphism was not associated with colorectal cancer risk. GSTM1 and GSTT1 null genotypes confer additional risk for colorectal cancer in Caucasian populations. (C) 2010 Elsevier Ltd. All rights reserved.