Genetic Polymorphisms of GSTM1, GSTT1, and GSTP1 with Prostate Cancer Risk: A Meta-Analysis of 57 Studies

Abstract

Background and ObjectivesThe GSTM1, GSTT1 and GSTP1 polymorphisms might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. However, studies investigating the association between GSTM1, GSTT1 or GSTP1 polymorphisms and prostate cancer (PCa) risk report conflicting results, therefore, we conducted a meta-analysis to re-examine the controversy.MethodsPublished literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI) were searched (updated to June 2, 2012). According to our inclusion criteria, studies that observed the association between GSTM1, GSTT1 or GSTP1 polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with GSTM1, GSTT1 and GSTP1 polymorphisms.ResultsFifty-seven studies involving 11313 cases and 12934 controls were recruited. The overall OR, which was 1.2854 (95% CI = 1.1405–1.4487), revealed a significant risk of PCa and GSTM1 null genotype, and the similar results were observed when stratified by ethnicity and control source. Further, the more important is that the present study first reported the high risks of PCa for people who with dual null genotype of GSTM1 and GSTT1 (OR = 1.4353, 95% CI = 1.0345–1.9913), or who with GSTT1 null genotype and GSTP1 A131G polymorphism (OR = 1.7335, 95% CI = 1.1067–2.7152). But no association was determined between GSTT1 null genotype (OR = 1.102, 95% CI = 0.9596–1.2655) or GSTP1 A131G polymorphism (OR = 1.0845, 95% CI = 0.96–1.2251) and the PCa risk.ConclusionsOur meta-analysis suggested that the people with GSTM1 null genotype, with dual null genotype of GSTM1 and GSTT1, or with GSTT1 null genotype and GSTP1 A131G polymorphism are associated with high risks of PCa, but no association was found between GSTT1 null genotype or GSTP1 A131G polymorphism and the risk of PCa. Further rigorous analytical studies are highly expected to confirm our conclusions and assess gene-environment interactions with PCa risk.

Glutathione S Transferases: Biochemistry, Polymorphism and Role in Colorectal Carcinogenesis

“…These SNPs affect the functioning of GST enzymes at the gene level as well as protein level, thereby influencing the detoxification process of carcinogens, and consequently, the level of DNA damage; thus it may have an indirect effect on the risk of development of cancer [64]. Multiple studies have been carried out from time to time to assess the impact of GST gene polymorphisms in colorectal cancer development and progression (Table 4).…”

GSTM1 gene polymorphism and the risk of colorectal cancer in a Saudi Arabian population

“…GSTM1 gene polymorphisms may exert an effect on the functioning of enzymes encoded by this gene through the change in both gene expression level and the activity of the protein itself. Thus, GSTM1 has an influence on the detoxification of carcinogens, and consequently, the level of DNA damage; in this way, an individual's susceptibility to toxins and carcinogens can vary owing to genetic variations that also affect the toxicity and effectiveness of particular drugs (Gong et al, 2012). The polymorphism of the GSTM1 gene observed in the human population comprises a hereditary homozygous deletion (null/null), a deletion of a gene fragment, resulting in a deficiency in the protein product, which is related to the total loss of enzymatic activity (Gong et al, 2012).…”

“…Thus, GSTM1 has an influence on the detoxification of carcinogens, and consequently, the level of DNA damage; in this way, an individual's susceptibility to toxins and carcinogens can vary owing to genetic variations that also affect the toxicity and effectiveness of particular drugs (Gong et al, 2012). The polymorphism of the GSTM1 gene observed in the human population comprises a hereditary homozygous deletion (null/null), a deletion of a gene fragment, resulting in a deficiency in the protein product, which is related to the total loss of enzymatic activity (Gong et al, 2012). The GSTM1 null genotype seems to be related to a low capacity for detoxification of selected xenobiotics and a reduced capability for controlling oxidative stress, which is equivalent to the damage to the cell caused by free radical activity (Wei et al, 2012).…”

Review GST genes polymorphisms and the risk of colorectal cancer development

“…In this way it has an influence on the possibility of detoxification of carcinogens, and consequently, the level of DNA damage; thus it may have an indirect effect on the risk of development of cancer [6]. …”