Glutathione S-transferase T1 gene polymorphism and colorectal cancer risk: An updated analysis

摘要

Background and objective: 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. Methods: 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. Results: 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. Conclusions: 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.