Gene polymorphisms of biotransforming enzymes (GSTs) and their association with lung cancer in the Slovakian population

Abstract

ObjectiveThe aim of present study was to present the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, and P1) and to investigate the association of these polymorphisms with lung cancer risk in the Slovakian population.Material and methodsThe study encompassed 160 lung cancer cases and 220 controls. DNA was extracted from peripheral blood leukocytes, and the polymorphisms of GSTM1, GSTT1 and GSTP1 enzymes were determined by PCR-based methods. We determined the genotype distribution of all these genes and their combinations. The association between specific genotypes and the development of lung cancer were examined using logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI).ResultsWe found that the GSTM1 null genotype (OR = 1.6; 95% CI = 1.03-2.4; χ2 = 4.08, and P = 0.04) was associated with elevated risk. A significant correlation also was found for the combined genotypes of GSTM1 null and GSTP1 Ile/Val and Val/Val (OR = 2.01; 95% CI = 1.1-6.1; χ2 = 3.6, and P = 0.02) and GSTM1 null and GSTT1 positive (OR = 2.00; 95% CI = 1.2-3.2; χ2 = 7.3, and P = 0.006).ConclusionsWe conclude that the genotype of metabolizing enzymes and allelic combinations underscore the risk for lung cancer. Individual risk assessment may be further improved by increasing the number of polymorphisms studied and combining them with the traditional epidemiological risk factor.

Genetic polymorphisms of glutathione S-transferase M1 and T1, and evaluation of oxidative stress in patients with non-small cell lung cancer

“…Human cytosolic GST genes exhibit genetic polymorphisms, and many genetic polymorphisms lead to altered GST activities, which may be partially responsible for the individual host’s susceptibility to oxidative damage. Previous studies suggested that GSTM1 and GSTT1 null genotypes may be associated with increased susceptibility to lung cancer [ 15 , 16 ], but other studies have shown no associations between GSTM1 and T1 null genotypes for lung cancer risk [ 17 , 18 ]. In our results, we found that the frequencies of the GSTM1, T1, and M1/T1 null genotypes were significantly higher in the patient group than that in the control group.…”

“…GSTM1 (1p13) and GSTT1 (22q 11.2) genes, encoding for a μ-GST isoenzyme and a θ-GST isoenzyme, respectively, can be deleted, thereby causing a lack of the respective enzyme function [ 14 ]. Some previous studies suggested that GSTM1 and GSTT1 null genotypes may be associated with increased susceptibility to lung cancer [ 15 , 16 ], but other studies have shown that there no association between GSTM1 and T1 null genotypes for lung cancer risk [ 17 , 18 ].…”

Combined effects of glutathione S-transferase M1 and T1 polymorphisms on risk of lung cancer: evidence from a meta-analysis

“…It is possible that the effect sizes of genetic factors predisposing to human diseases are different in various ethnic populations [ 66 ]. Dzian et al [ 16 ], Matakova et al [ 18 ], and Cajas-Salazar et al [ 27 ] suggested that the combined effects of GSTM1 and GSTT1 polymorphisms increased lung cancer risk in Caucasians. Chen et al [ 22 ], Liang KC et al [ 56 ], Cao YF et al [ 45 ], Pan et al [ 39 ], Piao et al [ 40 ], and Zhang et al [ 38 ] suggested that the GSTM1 and GSTT1 polymorphisms in combination were associated with increased risk factors of lung cancer in Asians.…”

Candidate gene studies of diabetic retinopathy in human

“…Oxidative stress is strongly implicated in the pathogenesis of DR, therefore the role of detoxifying enzymes, such as glutathione S-transferases (GST), was considered in the development of DR. Studies have shown that GSTT1 -null genotype is found more frequently in the cases with DR in Caucasians patients with T2DM compared to controls, so the GSTT1 -null genotype can be a risk factor for DR The individuals homozygous for the GSTT1 -null allele had more generalized vasculopathy that leads to increased risk of sight threatening DR. In contrast, the GSTM1 -null genotype may confer protection against development of DR in people with T2DM [67], but at the same time this polymorphism confers elevated risk for lung cancer [134]. There are reports that deficiency in GSTM1 leads to slower excretion of isothiocyanates.…”