An updating meta‐analysis of the GSTM1, GSTT1, and GSTP1 polymorphisms and prostate cancer: A HuGE Review

Abstract

It has been postulated that individuals with GSTM1, GSTT1 deficiency and, GSTP1 (105Ile/Val transition) have increased susceptibility to carcinogens and are more likely to develop prostate cancer. In recent years, GST status has been extensively studied as a prostate cancer risk factor; however, the results are inconsistent. To re-examine this controversy, we have undertaken an updating meta-analysis of 29 studies with GSTM1 genotyping (4,564 prostate cancer cases and 5,464 controls), 22 studies with GSTT1 genotyping (3,837 cases and 4,552 controls), and 24 studies with GSTP1 genotyping (5,301 cases and 5,621 controls). The random effects odds ratio was 1.33 [95% confidence interval (95% CI): 1.15, 1.55; I(2) = 68.9%, P for heterogeneity = 0.00] for the GSTM1 null versus present genotype and 1.05 (95% CI: 0.86, 1.27; I(2) = 68.2%, P for heterogeneity = 0.00) for the GSTT1 null versus present genotype, and 1.06 (95% CI: 0.91, 1.24; I(2) = 71.5%, P for heterogeneity = 0.00) for the GSTP1-Val versus GSTP1-Ile allele. For GSTM1 polymorphism, similar results reached in Caucasians and Asians, with exception for Africans. No association between GSTT1 or GSTP1 polymorphisms and prostate cancer risk was detected in different racial. In conclusion, the major finding of our study suggested that GSTM1 polymorphism conferred an increasing risk of prostate cancer on a wide population basis, however, no relationship was found between GSTT1 and GSTP1 status and the risk of prostate cancer.

Glutathione S-transferase M1 and T1 polymorphisms and cervical cancer risk: A meta-analysis

“…Thus, the GSTM1 and GSTT1 polymorphisms may exert different effects in different kinds of cancers and those various gene-variant associations may result from the different mechanisms of carcinogenesis among different cancers. Zhou et al [45] found that the GSTM1 polymorphism was associated with an increasing risk of nasopharyngeal cancer, but the GSTT1 polymorphism was not, which was the same with Mo et al' [46] results on prostate cancer risk and our results on CC risk. These results further confirmed the probability of our conclusions.…”

“…GST genetic polymorphisms have been extensively studied and several meta-analyses combining data from multiple stud-ies have been published to investigate the associations between GST polymorphisms and various cancers [42][43][44][45][46]. Wang et al suggested the null genotypes of GSTM1 and GSTT1 were both associated with increased hepatocellular carcinoma risk [42].…”

Impact of Tobacco on Glutathione S Transferase Gene Loci of Indian Ethnics

“…This observation of null type mutation in GSTT1 might have susceptible status or protective role to the individual for various diseases related to tobacco or their respective drug substrates. GSTT1 null type mutation leading to susceptibility for various cancers and diseases among the high frequency populations, reported earlier by various investigators (Lacko et al, 2009;Mo et al, 2009;Sam et al, 2009;Chuang et al, 2011;Kumar et al, 2011) were not yet uniformly demonstrated. In our observation, the DNA adducts of tobacco were causing mutation in GSTT1 gene loci and nullifying its detrimental function in carcinogenic compound biotransformation ability.…”

“…Drug/Xenobiotic compound metabolizing enzymes are capable of regulating the removal of this exogenous and endogenous DNA adducts/carcinogens from the cell (Hecht, 2003;Lacko et al, 2009). The mutation observed in GSTM1 or T1 was a deletion mutation of null genotype and completely lost its functions to become susceptible to various cancers or diseases and further the inheritance of the same (Evans et al, 2004;Anantharaman et al, 2007;Mo et al, 2009;Sam et al, 2009;Amer et al, 2011;Chuang et al, 2011;Kumar et al, 2011). In this study, we investigated the impact of tobacco usage on drug/Xenobiotic compound metabolizing GST gene loci mutation.…”

“…The GSTT1 null type mutation might influence the susceptibility nature of the Gujarat population for various diseased status and cancerous conditions as mentioned by various investigators (Evans et al, 2004;Anantharaman et al, 2007;Mo et al, 2009;Sam et al, 2009;Amer et al, 2011;Chuang et al, 2011;Kumar et al, 2011). In addition these populations were not able to utilize the GSTT1 dependent drugs for their treatment.…”