Glutathione S–Transferase M1 Polymorphism and Sporadic Colorectal Cancer Risk: An Updating Meta-Analysis and HuGE Review of 36 Case-Control Studies

Purpose

Sporadic colorectal cancer (CRC) is considered to be a multifactorial disease, in which multiple exposures to endogenous factors interact with individual genetic background in a complex manner, resulting in modulation of the risk. The glutathione S-transferase M1 gene (GSTM1) is a particularly attractive candidate for CRC susceptibility because it codes an enzyme involved in the metabolism of environmental carcinogens. However, the epidemiological findings have been inconsistent.

Methods

To evaluate this association, we performed an extensive meta-analysis of 36 case-control studies (including 10,009 cases and 15,070 controls).

Results

Overall, the combined data showed that GSTM1 deficiency is associated with a marginal effect on CRC risk (odds ratio [OR] = 1.13; 95% confidence interval [CI]: 1.03–1.23; P for heterogeneity <0.001). When stratified by race and tumor site, significant results were only observed in Caucasians (OR = 1.14, 95% CI: 1.01–1.27; P for heterogeneity <0.001), whereas no increased risk was detected in other subgroups.

Conclusions

The findings of our study support the suggestion that GSTM1 polymorphism is associated with an increased risk of CRC, especially in the Caucasian population. Further investigation into the association between GSTM1 polymorphism and the risk of CRC is warranted and should include larger sample sizes and other genetic polymorphisms in metabolism of environmental carcinogens.

Key words: Glutathione S-Transferase, Colorectal Cancer, Meta-Analysis, Epidemiology

Selected Abbreviations and Acronyms: GSTM1, glutathione S-transferase M1 [gene], HNPCC, hereditary nonpolyposis colorectal cancer, FAP, familial adenomatous polyposis coli, CRC, colorectal cancer, SCA, sporadic colorectal adenocarcinoma, CI, confidence interval, OR, odds ratio