Glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk: A meta-analysis and HuGE review

Abstract

Colorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. Its development is influenced by both environmental and genetic factors. The glutathione S-transferase P1 gene ( GSTP1) is a particularly attractive candidate for colorectal cancer susceptibility because it codes the enzyme involved in the metabolism of environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs). However, epidemiologic findings have been inconsistent. To investigate a putative association of GSTP1 Ile105Val polymorphism with the risk of colorectal cancer, we performed a meta-analysis and HuGE review of 16 published case-control studies (involving a total of 4386 colorectal cancer patients and 7127 controls). We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, the comparison of Val versus Ile allele showed no differential susceptibility to colorectal cancer (OR = 0.98, 95% CI: 0.92–1.04). A protective effect was found in recessive, with an OR of 0.86 (95% CI: 0.76–0.98). Whereas no significant association was observed in either dominant or codominant model. In stratified subgroup analysis, no effect of Val allele was seen in subjects of Caucasian and Asian descent, and in healthy and hospital controls. In conclusion, the meta-analysis suggests that the GSTP1 Ile105Val polymorphism is unlikely to increase considerably the risk of sporadic colorectal cancer, and it should be confirmed in further studies.