Glutathione S-transferase M1 gene polymorphism is related to COPD in patients with non-small-cell lung cancer.
OBJECTIVE
Oxidative stress contributes to the development of both lung cancer and chronic obstructive pulmonary disease (COPD). Antioxidative enzymes may protect against such damage. We hypothesized that genetic variations in glutathione S-transferase M1 and/or T1 genes (GSTM1 and GSTT1, respectively) may influence susceptibility to COPD in patients with non-small-cell lung cancer.


METHODS
The polymorphisms in GSTM1 and GSTT1 genes were examined in 110 patients (age: 63+/-1 years) with newly diagnosed non-small-cell lung cancer using the polymerase chain reaction. Respiratory function was assessed by bodyplethysmography.


RESULTS
In the GSTM1 null (-/-) genotype, both FEV1 and FEV1/FVC were significantly lower than in the GSTM1 plus genotype (GSTM1 -/+ or +/+) (75.8+/-2.5 versus 86.6+/-3.6%, p<0.02; 69.1+/-1.6 versus 77.0+/-2.4, p<0.01, respectively). Among the patients with GSTM1 null genotype, 49% suffered from COPD as opposed to 21% of patients with GSTM1 plus genotype. In contrast, no differences were seen in FEV1 or FEV1/FVC when comparing patients with GSTT1 null genotype and GSTT1 plus genotype (81.4+/-4.9 versus 79.3+/-2.3, p=NS; 71.1+/-2.9 versus 72.2+/-1.6, p=NS). Multiple stepwise regression analysis identified the GSTM1 genotype (p<0.02) as a significant independent predictor of FEV1 in this group of patients.


CONCLUSIONS
The present study suggests that in patients with non-small-cell lung cancer the presence of at least one active allele in GSTM1 has a protective effect against the development of COPD.
Tkácová
Ruzena
R
Department of Tuberculosis and Respiratory Medicine, Faculty of Medicine, P. J. Safárik University, Kosice, Slovakia. rtkacova@hotmail.com
Salagovic
Ján
J
Ceripková
Marianna
M
Tkác
Ivan
I
Stubna
Ján
J
Kalina
Ivan
I
D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014797:Vital Capacity / Q000502:physiology
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1