Boccia Stefania, La Torre Giuseppe, Gianfagna Francesco, Mannocci Alice, Ricciardi Gualtiero
Institute of Hygiene, Catholic University of Sacred Heart, L.go F.Vito, 1-00168 Rome, Italy.
Mutagenesis. 2006 Mar;21(2):115-23. doi: 10.1093/mutage/gel005. Epub 2006 Mar 3.
To clarify the risk of gastric cancer associated with glutathione S-transferase T1 (GSTT1) status, a meta-analysis of published studies was performed. Eligible studies included all reports investigating an association between GSTT1 status and gastric cancer published before October 31, 2005. A qualitative scoring of papers was applied to evaluate the quality of the published data. The principal outcome measure was the odds ratio (OR) for the risk of gastric cancer associated with GSTT1 deletion status using a random effects model. Eighteen case-control studies detailing a possible association between the GSTT1 null genotype and gastric cancer were selected. Combining data from these studies, totalling 2508 cases and 4634 controls, a non-statistically significant OR for gastric cancer risk associated with GSTT1 deficiency emerged [OR = 1.09; 95% confidence interval (CI): 0.97-1.21; I(2) = 0%]. When only high-quality scored studies were considered, a statistically significant increased risk appeared (OR = 1.23; 95% CI: 1.04-1.45; I(2) = 0%), as well as considering only Caucasians (OR = 1.23; 95% CI: 1.03-1.56; I(2) = 0%). By pooling data from seven studies (319 cases and 656 controls) that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for gastric cancer (OR = 1.95, 95% CI: 1.42-2.67; I(2) = 0%) was detected for individuals with deletion mutations in both genes compared with wild-types. In conclusion, this meta-analysis suggests that the GSTT1 null genotype may slightly increase the risk of gastric cancer and that interaction between unfavourable GST genotypes may exist. Greater attention should, therefore, be paid to the design of future studies; the investigation of interactions among multiple genotypes and environmental exposures are justified to clarify GSTT1 null status influence on gastric cancer risk.
为了明确谷胱甘肽S-转移酶T1（GSTT1）状态与胃癌风险之间的关系，我们对已发表的研究进行了荟萃分析。符合条件的研究包括2005年10月31日前发表的所有关于GSTT1状态与胃癌关联的报告。我们采用论文质量定性评分来评估已发表数据的质量。主要结局指标是使用随机效应模型得出的与GSTT1缺失状态相关的胃癌风险比值比（OR）。我们选取了18项病例对照研究，这些研究详细阐述了GSTT1无效基因型与胃癌之间可能存在的关联。综合这些研究的数据，共计2508例病例和4634例对照，结果显示与GSTT1缺乏相关的胃癌风险的OR无统计学意义[OR = 1.09；95%置信区间（CI）：0.97 - 1.21；I(2) = 0%]。当仅考虑高质量评分的研究时，出现了统计学上显著增加的风险（OR = 1.23；95% CI：1.04 - 1.45；I(2) = 0%），仅考虑白种人时也是如此（OR = 1.23；95% CI：1.03 - 1.56；I(2) = 0%）。通过汇总7项研究（319例病例和656例对照）的数据，这些研究考虑了GSTT1和GSTM1基因型的组合，结果发现与野生型相比，两个基因均有缺失突变的个体患胃癌的风险有统计学意义的增加（OR = 1.95，95% CI：1.42 - 2.67；I(2) = 0%）。总之，这项荟萃分析表明，GSTT1无效基因型可能会略微增加胃癌风险，并且可能存在不利的GST基因型之间的相互作用。因此，未来的研究设计应给予更多关注；对多种基因型与环境暴露之间相互作用的研究对于阐明GSTT1无效状态对胃癌风险的影响是合理的。
