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Although smoking is regarded as the most important causal factor in chronic obstructive pulmonary disease (COPD), only 10-20% of smokers develop symptomatic COPD, which indicates the presence of genetic predisposing factors in its pathogenesis. This study investigates the association between gene polymorphysims of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149 patients and 150 healthy controls. Polymorphisms of GSTT1, GSTM1, and GSTP1 were genotyped using Real-Time PCR. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals between specific genotypes and COPD. There was no difference in the frequencies of the genotypes of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was significantly higher in the patients than in the controls (61.1% vs. 38%). GSTP1 Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when compared to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we suggest that the Val allele of GSTP1 may have a protective effect for development of COPD. Furthermore, when we evaluated the association between GSTP1 genes and smoking status, smokers with the GSTP1 Ile allele had an increased risk for the development of COPD. Among the combinations of the genotypes, the combination of GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased risk (12-fold) of COPD. Thus to explain the ethiopathogenesis of COPD, investigation of a single gene family is inadequate. Based on our results and the previous data, further studies should be focused on the GSTP1 gene and the interactions with other genes such as polymorphisms of N-acetyltransferases, GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome P450.

The glutathione S-transferase (GST) supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to detect a possible association between polymorphisms at the GSTM1, GSTT1, and GSTP1 genes and the interaction with cigarette smoking and colorectal cancer incidence. We examined 181 patients with colorectal cancer and 204 controls. DNA was extracted from whole blood, and the GSTM1, GSTT1, and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler instrument. Associations between specific genotypes and the development of colorectal cancer were examined by use of logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer (OR = 1.62, 95% CI: 1.06–2.46). Also the risk of colorectal cancer associated with the GSTT1 null genotype was 1.64 (95% CI: 1.10–2.59). Statistically no differences were found between patients with colorectal cancer and control groups for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. In addition, the frequencies of the GSTM1 and GSTT1 deletion genotypes differed significantly between the cases and controls for current smokers; the GSTT1 null genotype especially is associated with a greater risk of colorectal cancer (OR = 2.44, 95% CI: 1.24–4.81). The GSTM1 and GSTT1 deletions were associated with an increased risk of developing a transverse or rectal tumor (OR = 1.86, 95% CI: 1.15–3.00; OR = 1.70, 95% CI: 1.02–2.84; respectively). The glutathione S-transferase polymorphisms were not associated with risk in patients stratified by age. The risk of colorectal cancer increased as putative high-risk genotypes increased for the combined genotypes of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity (OR = 2.69, 95% CI: 1.02–7.11). In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to different GST polymorphic enzymes are predisposing for colorectal cancer.