Jia Cheng-You, Liu Yu-Jin, Cong Xian-Ling, Ma Yu-Shui, Sun Ran, Fu Da, Lv Zhong-Wei
Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China.
Tumour Biol. 2014 Apr;35(4):3867-73. doi: 10.1007/s13277-013-1513-5. Epub 2013 Dec 15.
The glutathione S-transferases (GSTs) are a gene superfamily of phase II metabolic enzymes that has attracted a considerable attention as a candidate gene for renal cell carcinoma (RCC) based on its enzyme function as a key factor in biotransformation pathways. In the past decade, a number of case-control studies were conducted to investigate the association of GST genetic polymorphisms and RCC risk. However, studies on the association between GST (GSTM1, GSTT1, and GSTP1) polymorphisms and RCC remain to be conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 2,189 cases and 3,817 controls from 11 case-control studies was performed. Overall, the summarized odds ratio for RCC of the GSTM1 null and GSTT1 null polymorphisms was 1.02 (95% confidence interval (CI) 0.91-1.15, P = 0.70) and 1.28 (95% CI 0.96-1.72, P = 0.09), respectively. No significant results were observed in heterozygous and homozygous genotypes when compared with wild-type genotype for GSTP1 I105V polymorphism. However, the GSTM1-GSTT1 interaction analysis showed that the dual null genotype of GSTM1/GSTT1 was significantly associated with an increased RCC risk (odds ratio (OR) = 1.42, 95% CI 1.14-1.76, P = 0.001). In the stratified analyses by ethnicity, significant gene-disease association was obtained among Asians for GSTT1 and GSTP1 polymorphisms. In our meta-analysis, the associations between variations of GSTs and RCC may vary in different ethnic populations, and the interaction between unfavorable GST genotypes may exist.
谷胱甘肽S-转移酶（GSTs）是Ⅱ相代谢酶的一个基因超家族，基于其作为生物转化途径关键因子的酶功能，作为肾细胞癌（RCC）的候选基因已引起了相当大的关注。在过去十年中，进行了多项病例对照研究以调查GST基因多态性与RCC风险的关联。然而，关于GST（GSTM1、GSTT1和GSTP1）多态性与RCC之间关联的研究结果仍存在冲突。为了更精确地估计这种关系，对来自11项病例对照研究的2189例病例和3817例对照进行了荟萃分析。总体而言，GSTM1缺失和GSTT1缺失多态性的RCC汇总比值比分别为1.02（95%置信区间（CI）0.91 - 1.15，P = 0.70）和1.28（95%CI 0.96 - 1.72，P = 0.09）。对于GSTP1 I105V多态性，与野生型基因型相比，杂合子和纯合子基因型未观察到显著结果。然而，GSTM1 - GSTT1相互作用分析表明，GSTM1/GSTT1的双重缺失基因型与RCC风险增加显著相关（比值比（OR）= 1.42，95%CI 1.14 - 1.76，P = 0.001）。在按种族进行的分层分析中，亚洲人群中GSTT1和GSTP1多态性存在显著的基因 - 疾病关联。在我们的荟萃分析中，GSTs变异与RCC之间的关联在不同种族人群中可能有所不同，并且不利的GST基因型之间可能存在相互作用。
