Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 37, Guo Xue Road, Chengdu 610041, Sichuan Province, China.
Clin Res Hepatol Gastroenterol. 2013 Dec;37(6):626-35. doi: 10.1016/j.clinre.2013.04.007. Epub 2013 Jun 14.
The association between glutathione S-transferase T1 (GSTT1) gene polymorphisms and colorectal cancer (CRC) susceptibility is still controversial. In order to clarify the effect of GSTT1 genotype on the CRC risk, we carried out an updated meta-analysis of published case-control studies to provide more precise evidence.
Two investigators independently searched the databases of Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) up to October 15, 2012. Crude odds ratios (OR) and 95% confidence intervals (CI) were calculated to investigate the strength of the association in a fixed- or random-effects model depending on statistical heterogeneity.
Forty-six case-control studies with 15,373 colorectal cancer cases and 21,238 controls were included. Overall, the pooled results indicated that GSTT1 null genotype was significantly associated with increased CRC risk (OR=1.21, 95% CI=1.10-1.33). When stratifying for ethnicity and control sources, we also observed positive association between GSTT1 null genotype and increased risk of CRC. When stratifying by the location, we found there was a statistically significant association in the rectal cancer (OR=1.28, 95% CI=1.01-1.64), but not in colon cancer (OR=1.27, 95% CI=0.94-1.73). Subgroup analyses for Dukes stage, histological differentiation of CRC and smoking habit did not reveal any significant differences in genotype distribution. In addition, we observed a strong correlation between increased CRC risk and the combined GSTM1 and GSTT1 null genotype.
This meta-analysis suggests that the GSTT1 null genotype may contribute to increased risk of colorectal cancer. More well-designed studies based on larger population are needed to confirm our results.
谷胱甘肽 S-转移酶 T1（GSTT1）基因多态性与结直肠癌（CRC）易感性之间的关系仍存在争议。为了阐明 GSTT1 基因型对 CRC 风险的影响，我们对已发表的病例对照研究进行了更新的荟萃分析，以提供更准确的证据。
两名研究者独立检索了 Pubmed、EMBASE 和中国知网（CNKI）数据库，检索时间截至 2012 年 10 月 15 日。根据统计学异质性，采用固定效应模型或随机效应模型计算粗比值比（OR）和 95%置信区间（CI），以评估关联的强度。
共纳入 46 项病例对照研究，包括 15373 例结直肠癌病例和 21238 例对照。总体而言，汇总结果表明 GSTT1 缺失基因型与 CRC 风险增加显著相关（OR=1.21，95%CI=1.10-1.33）。按种族和对照来源分层时，我们也观察到 GSTT1 缺失基因型与 CRC 风险增加之间存在正相关。按部位分层时，我们发现直肠癌（OR=1.28，95%CI=1.01-1.64）存在统计学显著相关性，但结肠癌（OR=1.27，95%CI=0.94-1.73）无相关性。对 Dukes 分期、CRC 组织学分化和吸烟习惯的亚组分析未发现基因型分布有显著差异。此外，我们观察到 CRC 风险增加与 GSTT1 和 GSTT1 联合缺失基因型之间存在很强的相关性。
本荟萃分析表明，GSTT1 缺失基因型可能导致结直肠癌风险增加。需要更多基于较大人群的设计良好的研究来证实我们的结果。
