Pooled Analysis and Meta-analysis of Glutathione S-Transferase M1 and Bladder Cancer: A HuGE Review

Abstract

Smoking is a known risk factor for bladder cancer. The product of the GSTM1 gene, glutathione S-transferase M1 (GSTM1), is involved in the detoxification of polycyclic aromatic hydrocarbons found in tobacco smoke; a homozygous deletion of this gene in approximately 50% of Caucasians and Asians results in a lack of GSTM1 enzyme activity. Most studies examining the relation between bladder cancer and GSTM1 have reported an increased risk associated with a lack of GSTM1 activity. The authors performed meta- and pooled analyses of published and unpublished, case-control, genotype-based studies that examined this association (17 studies, 2,149 cases, 3,646 controls) and excluded studies conducted in populations with a high prevalence of exposure to known bladder cancer risk factors other than tobacco smoke. Using random effects models in the meta-analysis, the authors obtained a summary odds ratio of 1.44 (95% confidence interval (CI): 1.23, 1.68) for GSTM1 null status with all studies included. Results from studies with at least 100 cases and 100 controls produced a summary odds ratio of 1.42 (95% CI: 1.26, 1.60). Pooled analyses using original data sets from 10 studies (1,496 cases and 1,444 controls) and adjusting for age, sex, and race produced similar results. There was no evidence of multiplicative interaction between the GSTM1 null genotype and ever smoking in relation to bladder cancer, although there was a suggestion of additive interaction (additive interaction = 0.45, 95% CI: -0.03, 0.93). These results indicate that, among populations studied to date, GSTM1 null status is associated with a modest increase in the risk of bladder cancer.

Risk Effects of GST Gene Polymorphisms in Patients with Acute Myeloid Leukemia: A Prospective Study

“…The null genotype of GSTM1 and GSTT1 and GSTP Val/ Val genotype may lower the expression and activity of genotypes, and these genotypes are known to be associated with increasing incidence of certain cancers, such as head and neck, lung and bladder cancer (Benhamou et al, 2002;Engel et al, 2003;Hashibe et al, 2003). The main reason might be the inefficient carcinogen detoxification and therefore a higher risk of developing cancer.…”

Cytogenetic damage and genetic variants in the individuals susceptible to arsenic‐induced cancer through drinking water

“…[25][26][27][28][29][30] However, the results are not unequivocal. We have examined the association, if any, between GST genotypes with arsenic-induced skin lesions.…”

“…24 Genetic variants of GST, alone or in combination with other genetic variations and environmental factors, were associated with a number of multifactorial diseases and conditions, such as smoking-related tumors, bladder cancer, colorectal cancer; esophageal cancer, myelodysplastic syndrome and leukemia, liver and renal diseases, and several other diseases like chronic obstructive pulmonary disease, bronchial asthma and solar keratosis. [25][26][27][28][29][30] GSTP1 is widely expressed in normal epithelium and is also involved in the detoxification of carcinogens in different tissues. 31,32 GSTP1 is overexpressed in tumors compared to normal tissues and has a role in cellular protection against oxidative stress.…”

Role of GSTT1 deletion in DNA oxidative damage by exposure to polycyclic aromatic hydrocarbons in humans

“…Individual case control studies, as well as pooled and meta analyses have confirmed this hypothesis to some extent, so that for example the deletion of GSTM1 variant was found to be associated with various cancer types, both alone and in combination with other genetic polymorphisms. [7][8][9][10] Careful analysis of the literature reveals a much more murky picture for the GSTT1 gene than for GSTM1. Although one group reported GSTT1 to be a risk factor for lung cancer, 11 the majority of studies have found no association between GSTT1 deletion and cancer as shown by a meta and pooled analysis, 12 and in general there are more negative findings for this variant than for the GSTM1 deletion.…”